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1. The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors

Author: Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, AA, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Davies, JA, Abbracchio, MP, Abraham, G, Agoulnik, A, Alexander, W, Al-hosaini, K, Back, M, Baker, JG, Barnes, NM, Bathgate, R, Beaulieu, J-M, Beck-Sickinger, AG, Behrens, M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Cox, HM, Csaba, Z, Dahlgren, C, Dent, G, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, Garelja, ML, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gratz, L, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Herr, D, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Larhammar, D, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Malfacini, D, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, PM, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Smith, CM, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PBMWM, Tirupula, K, Toll, L, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, and Ye, RD
Abstract: The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Published: 2023

2. THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview

Author: Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil V, Peters, John A, Faccenda, Elena, Harding, Simon D, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, O Peter, Cidlowski, John A, Christopoulos, Arthur, Davenport, Anthony P, Fabbro, Doriano, Spedding, Michael, Striessnig, Jörg, Davies, Jamie A, Abbracchio, M‐P, Aldrich, R, Al‐Hosaini, K, Arumugam, TV, Attali, B, Bäck, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Bettler, B, Biel, M, Birdsall, NJ, Blaho, V, Boison, D, Bräuner‐osborne, H, Bröer, S, Bryant, C, Burnstock, G, Calo, G, Catterall, WA, Ceruti, S, Chan, SL, Chandy, KG, Chazot, P, Chiang, N, Chun, JJ, Chung, J‐J, Clapham, DE, Clapp, L, Connor, MA, Cox, HM, Davies, P, Dawson, PA, Decaen, P, Dent, G, Doherty, P, Douglas, SD, Dubocovich, ML, Fong, TM, Fowler, CJ, Frantz, A, Fuller, P, Fumagalli, M, Futerman, AH, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Goudet, C, Gregory, K, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hamann, J, Hammond, JR, Hancox, JC, Hanson, J, Hanukoglu, I, Hay, DL, Hobbs, AJ, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Irving, AJ, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, MF, Jensen, R, Jockers, R, Kaczmarek, LK, Kanai, Y, Karnik, S, Kellenberger, S, Kemp, S, Kennedy, C, Kerr, ID, Kihara, Y, Kukkonen, J, Larhammar, D, Leach, K, Lecca, D, Leeman, S, Leprince, J, Lolait, SJ, Macewan, D, Maguire, JJ, Marshall, F, Mazella, J, Mcardle, CA, Michel, MC, Miller, LJ, Mitolo, V, Mizuno, H, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J‐L, Nerbonne, J, Nichols, CG, Norel, X, Offermanns, S, Palmer, LG, Panaro, MA, Papapetropoulos, A, Perez‐reyes, E, Pertwee, RG, Pintor, S, Pisegna, JR, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ramachandran, R, Ren, D, Rondard, P, Ruzza, C, Sackin, H, Sanger, G, Sanguinetti, MC, Schild, L, Schiöth, H, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Singh, KD, Slesinger, PA, Snutch, TP, Sobey, CG, Stewart, G, Stoddart, LA, Summers, RJ, Szabo, C, Thwaites, D, Toll, L, Trimmer, JS, Tucker, S, Vaudry, H, Verri, T, Vilargada, J‐P, Waldman, SA, Ward, DT, Waxman, SG, Wei, AD, Willars, GB, Wong, SS, Woodruff, TM, Wulff, H, Ye, RD, Yung, Y, and Zajac, J‐M
Published: 2017
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3. Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A1 Receptor in Living Cells

Author: Comeo, E, Trinh, P, Nguyen, AT, Nowell, CJ, Kindon, ND, Soave, M, Stoddart, LA, White, JM, Hill, SJ, Kellam, B, Halls, ML, May, LT, Scammells, PJ, Comeo, E, Trinh, P, Nguyen, AT, Nowell, CJ, Kindon, ND, Soave, M, Stoddart, LA, White, JM, Hill, SJ, Kellam, B, Halls, ML, May, LT, and Scammells, PJ
Abstract: The adenosine A1 receptor (A1AR) is a G-protein-coupled receptor (GPCR) that provides important therapeutic opportunities for a number of conditions including congestive heart failure, tachycardia, and neuropathic pain. The development of A1AR-selective fluorescent ligands will enhance our understanding of the subcellular mechanisms underlying A1AR pharmacology facilitating the development of more efficacious and selective therapies. Herein, we report the design, synthesis, and application of a novel series of A1AR-selective fluorescent probes based on 8-functionalized bicyclo[2.2.2]octylxanthine and 3-functionalized 8-(adamant-1-yl) xanthine scaffolds. These fluorescent conjugates allowed quantification of kinetic and equilibrium ligand binding parameters using NanoBRET and visualization of specific receptor distribution patterns in living cells by confocal imaging and total internal reflection fluorescence (TIRF) microscopy. As such, the novel A1AR-selective fluorescent antagonists described herein can be applied in conjunction with a series of fluorescence-based techniques to foster understanding of A1AR molecular pharmacology and signaling in living cells.
Published: 2021

4. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

Author: Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, Ye, RD, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Southan, C, Davies, JA, Abbracchio, MP, Alexander, W, Al-hosaini, K, Baeck, M, Barnes, NM, Bathgate, R, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Boulay, F, Bousquet, C, Braeuner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, K, Ceruti, S, Chazot, P, Chiang, N, Chini, B, Chun, J, Cianciulli, A, Civelli, O, Clapp, LH, Couture, R, Csaba, Z, Dahlgren, C, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, EJ, Fong, T, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gerard, C, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, DL, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, IJzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kitazawa, T, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Li, XX, Williams, TL, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, LJ, Mitolo, V, Mouillac, B, Mueller, CE, Murphy, P, Nahon, J-L, Ngo, T, Norel, X, Nyimanu, D, Ocarroll, A-M, Offermanns, S, Panaro, MA, Parmentier, M, Pertwee, RG, Pin, J-P, Prossnitz, ER, Quinn, M, Ramachandran, R, Ray, M, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, GJ, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, VP, Thal, D, Thomas, WW, Timmermans, PMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Valant, C, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Wang, JM, Ward, DT, Wester, H-J, Willars, GB, Woodruff, TM, Yao, C, and Ye, RD
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Published: 2021

5. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors

Author: Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Arumugam, TV, Bennett, A, Sjogren, B, Sobey, C, Wong, SS, Abbracchio, MP, Alexander, W, Al-hosaini, K, Back, M, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chun, J, Cianciulli, A, Clapp, LH, Couture, R, Csaba, Z, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, E, Fong, TM, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, D, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, L, Mitolo, V, Mouillac, B, Murphy, PM, Nahon, J-L, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Pertwee, RG, Pin, J-P, Prossnitz, E, Ramachandran, R, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, G, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, V, Thomas, W, Timmermans, PBMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, Aldrich, RW, Becirovic, E, Biel, M, Catterall, WA, Conner, AC, Davies, P, Delling, M, Di Virgilio, F, Falzoni, S, George, C, Goldstein, SAN, Grissmer, S, Ha, K, Hammelmann, V, Hanukoglu, I, Jarvis, M, Jensen, AA, Kaczmarek, LK, Kellenberger, S, King, B, Lynch, JW, Perez-Reyes, E, Plant, LD, Rash, LD, Ren, D, Sivilotti, LG, Smart, TG, Snutch, TP, Tian, J, Van den Eynde, C, Vriens, J, Wei, AD, Winn, BT, Wulff, H, Xu, H, Yue, L, Zhang, X, Zhu, M, Coons, L, Fuller, P, Korach, KS, Young, M, Bryant, C, Farndale, RW, Hobbs, A, Jarvis, GE, MacEwan, D, Monie, TP, Waldman, S, Beuve, A, Boison, D, Brouckaert, P, Burnett, JC, Burns, K, Dessauer, C, Friebe, A, Garthwaite, J, Gertsch, J, Helsby, N, Izzo, AA, Koesling, D, Kuhn, M, Ostrom, R, Papapetropoulos, A, Potter, LR, Pyne, NJ, Pyne, S, Russwurm, M, Schmidt, HHHW, Seifert, R, Stasch, J-P, Szabo, C, van der Stelt, M, van der Vliet, A, Watts, V, Anderson, CMH, Broer, S, Dawson, P, Hagenbuch, B, Hammond, JR, Hancox, J, Inui, K-I, Kanai, Y, Kemp, S, Thwaites, DT, Verri, T, Alexander, SPH, Christopoulos, A, Davenport, AP, Kelly, E, Mathie, A, Peters, JA, Veale, EL, Armstrong, JF, Faccenda, E, Harding, SD, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Arumugam, TV, Bennett, A, Sjogren, B, Sobey, C, Wong, SS, Abbracchio, MP, Alexander, W, Al-hosaini, K, Back, M, Beaulieu, J-M, Bernstein, KE, Bettler, B, Birdsall, NJM, Blaho, V, Bousquet, C, Brauner-Osborne, H, Burnstock, G, Calo, G, Castano, JP, Catt, KJ, Ceruti, S, Chazot, P, Chiang, N, Chun, J, Cianciulli, A, Clapp, LH, Couture, R, Csaba, Z, Dent, G, Singh, KD, Douglas, SD, Dournaud, P, Eguchi, S, Escher, E, Filardo, E, Fong, TM, Fumagalli, M, Gainetdinov, RR, de Gasparo, M, Gershengorn, M, Gobeil, F, Goodfriend, TL, Goudet, C, Gregory, KJ, Gundlach, AL, Hamann, J, Hanson, J, Hauger, RL, Hay, D, Heinemann, A, Hollenberg, MD, Holliday, ND, Horiuchi, M, Hoyer, D, Hunyady, L, Husain, A, Ijzerman, AP, Inagami, T, Jacobson, KA, Jensen, RT, Jockers, R, Jonnalagadda, D, Karnik, S, Kaupmann, K, Kemp, J, Kennedy, C, Kihara, Y, Kozielewicz, P, Kreienkamp, H-J, Kukkonen, JP, Langenhan, T, Leach, K, Lecca, D, Lee, JD, Leeman, SE, Leprince, J, Lolait, SJ, Lupp, A, Macrae, R, Maguire, J, Mazella, J, McArdle, CA, Melmed, S, Michel, MC, Miller, L, Mitolo, V, Mouillac, B, Murphy, PM, Nahon, J-L, Norel, X, Nyimanu, D, O'Carroll, A-M, Offermanns, S, Panaro, MA, Pertwee, RG, Pin, J-P, Prossnitz, E, Ramachandran, R, Reinscheid, RK, Rondard, P, Rovati, GE, Ruzza, C, Sanger, G, Schoeneberg, T, Schulte, G, Schulz, S, Segaloff, DL, Serhan, CN, Stoddart, LA, Sugimoto, Y, Summers, R, Tan, V, Thomas, W, Timmermans, PBMWM, Tirupula, K, Tulipano, G, Unal, H, Unger, T, Vanderheyden, P, Vaudry, D, Vaudry, H, Vilardaga, J-P, Walker, CS, Ward, DT, Wester, H-J, Willars, GB, Williams, TL, Woodruff, TM, Yao, C, Aldrich, RW, Becirovic, E, Biel, M, Catterall, WA, Conner, AC, Davies, P, Delling, M, Di Virgilio, F, Falzoni, S, George, C, Goldstein, SAN, Grissmer, S, Ha, K, Hammelmann, V, Hanukoglu, I, Jarvis, M, Jensen, AA, Kaczmarek, LK, Kellenberger, S, King, B, Lynch, JW, Perez-Reyes, E, Plant, LD, Rash, LD, Ren, D, Sivilotti, LG, Smart, TG, Snutch, TP, Tian, J, Van den Eynde, C, Vriens, J, Wei, AD, Winn, BT, Wulff, H, Xu, H, Yue, L, Zhang, X, Zhu, M, Coons, L, Fuller, P, Korach, KS, Young, M, Bryant, C, Farndale, RW, Hobbs, A, Jarvis, GE, MacEwan, D, Monie, TP, Waldman, S, Beuve, A, Boison, D, Brouckaert, P, Burnett, JC, Burns, K, Dessauer, C, Friebe, A, Garthwaite, J, Gertsch, J, Helsby, N, Izzo, AA, Koesling, D, Kuhn, M, Ostrom, R, Papapetropoulos, A, Potter, LR, Pyne, NJ, Pyne, S, Russwurm, M, Schmidt, HHHW, Seifert, R, Stasch, J-P, Szabo, C, van der Stelt, M, van der Vliet, A, Watts, V, Anderson, CMH, Broer, S, Dawson, P, Hagenbuch, B, Hammond, JR, Hancox, J, Inui, K-I, Kanai, Y, Kemp, S, Thwaites, DT, and Verri, T
Abstract: The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Published: 2019

6. The Concise Guide to PHARMACOLOGY 2013/14: overview

Author: Alexander, SP, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, McGrath, JC, Catterall, WA, Spedding, M, Peters, JA, Harmar, AJ, CGTP Collaborators, Abul-Hasn, N, Anderson, CM, Araiksinen, MS, Arita, M, Arthofer, E, Barker, EL, Barratt, C, Barnes, NM, Bathgate, R, Beart, PM, Belelli, D, Bennett, AJ, Birdsall, NJ, Boison, D, Bonner, TI, Brailsford, L, Bröer, S, Brown, P, Calo, G, Carter, WG, Chan, SL, Chao, MV, Chiang, N, Christopoulos, A, Chun, JJ, Cidlowski, J, Clapham, DE, Cockcroft, S, Connor, MA, Cox, HM, Cuthbert, A, Dautzenberg, FM, Davenport, AP, Dawson, PA, Dent, G, Dijksterhuis, JP, Dollery, CT, Dolphin, AC, Donowitz, M, Dubocovich, ML, Eiden, L, Eidne, K, Evans, BA, Fabbro, D, Fahlke, C, Farndale, R, Fitzgerald, GA, Fong, TM, Fowler, CJ, Fry, JR, Funk, CD, Futerman, AH, Ganapathy, V, Gaisnier, B, Gershengorn, MA, Goldin, A, Goldman, ID, Gundlach, AL, Hagenbuch, B, Hales, TG, Hammond, JR, Hamon, M, Hancox, JC, Hauger, RL, Hay, DL, Hobbs, AJ, Hollenberg, MD, Holliday, ND, Hoyer, D, Hynes, NA, Inui, KI, Ishii, S, Jacobson, KA, Jarvis, GE, Jarvis, MF, Jensen, R, Jones, CE, Jones, RL, Kaibuchi, K, Kanai, Y, Kennedy, C, Kerr, ID, Khan, AA, Klienz, MJ, Kukkonen, JP, Lapoint, JY, Leurs, R, Lingueglia, E, Lippiat, J, Lolait, SJ, Lummis, SC, Lynch, JW, MacEwan, D, Maguire, JJ, Marshall, IL, May, JM, McArdle, CA, Michel, MC, Millar, NS, Miller, LJ, Mitolo, V, Monk, PN, Moore, PK, Moorhouse, AJ, Mouillac, B, Murphy, PM, Neubig, RR, Neumaier, J, Niesler, B, Obaidat, A, Offermanns, S, Ohlstein, E, Panaro, MA, Parsons, S, Pwrtwee, RG, Petersen, J, Pin, JP, Poyner, DR, Prigent, S, Prossnitz, ER, Pyne, NJ, Pyne, S, Quigley, JG, Ramachandran, R, Richelson, EL, Roberts, RE, Roskoski, R, Ross, RA, Roth, M, Rudnick, G, Ryan, RM, Said, SI, Schild, L, Sanger, GJ, Scholich, K, Schousboe, A, Schulte, G, Schulz, S, Serhan, CN, Sexton, PM, Sibley, DR, Siegel, JM, Singh, G, Sitsapesan, R, Smart, TG, Smith, DM, Soga, T, Stahl, A, Stewart, G, Stoddart, LA, Summers, RJ, Thorens, B, Thwaites, DT, Toll, L, Traynor, JR, Usdin, TB, Vandenberg, RJ, Villalon, C, Vore, M, Waldman, SA, Ward, DT, Willars, GB, Wonnacott, SJ, Wright, E, Ye, RD, Yonezawa, A, and Zimmermann, M
Abstract: The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2013

7. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Transporters

Author: Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13355/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

8. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Ligand-gated ion channels

Author: Alexander, SPH, Peters, JA, Kelly, E, Marrion, N, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Peters, JA, Kelly, E, Marrion, N, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13349/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

9. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Nuclear hormone receptors

Author: Alexander, SPH, Cidlowski, JA, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Cidlowski, JA, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13352/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

10. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Overview

Author: Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Buneman, OP, Catterall, WA, Cidlowski, JA, Davenport, AP, Fabbro, D, Fan, G, McGrath, JC, Spedding, M, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Buneman, OP, Catterall, WA, Cidlowski, JA, Davenport, AP, Fabbro, D, Fan, G, McGrath, JC, Spedding, M, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

11. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors

Author: Alexander, SPH, Davenport, AP, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Davenport, AP, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

12. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Catalytic receptors

Author: Alexander, SPH, Fabbro, D, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Fabbro, D, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

13. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Enzymes

Author: Alexander, SPH, Fabbro, D, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Fabbro, D, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13354/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

14. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Other ion channels

Author: Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13351/full. Other ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

15. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Voltage-gated ion channels

Author: Alexander, SPH, Catterall, WA, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, Zajac, J-M, Alexander, SPH, Catterall, WA, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ, Sharman, JL, Southan, C, Davies, JA, Aldrich, R, Attali, B, Back, M, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Brauner-Osborne, H, Broeer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J-J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hebert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, McArdle, CA, McDonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J-L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez-Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M-J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J-P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J-M
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13350/full. Voltage-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
Published: 2015

16. [Untitled]

Author: Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil, Peters, John A, Benson, Helen E, Faccenda, Elena, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, O Peter, Catterall, William A, Cidlowski, John A, Davenport, Anthony P, Fabbro, Doriano, Fan, Grace, McGrath, John C, Spedding, Michael, Davies, Jamie A, Aldrich, R, Attali, B, Bäck, Ml, Barnes, NM, Bathgate, R, Beart, PM, Becirovic, E, Biel, M, Birdsall, NJ, Boison, D, Bräuner‐Osborne, H, Bröer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, SL, Chandy, KG, Chiang, N, Christakos, S, Christopoulos, A, Chun, JJ, Chung, J‐J, Clapham, DE, Connor, MA, Coons, L, Cox, HM, Dautzenberg, FM, Dent, G, Douglas, SD, Dubocovich, ML, Edwards, DP, Farndale, R, Fong, TM, Forrest, D, Fowler, CJ, Fuller, P, Gainetdinov, RR, Gershengorn, MA, Goldin, A, Goldstein, SAN, Grimm, SL, Grissmer, S, Gundlach, AL, Hagenbuch, B, Hammond, JR, Hancox, JC, Hartig, S, Hauger, RL, Hay, DL, Hébert, T, Hollenberg, AN, Holliday, ND, Hoyer, D, Ijzerman, AP, Inui, KI, Ishii, S, Jacobson, KA, Jan, LY, Jarvis, GE, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, LK, Kanai, Y, Kang, HS, Karnik, S, Kerr, ID, Korach, KS, Lange, CA, Larhammar, D, Leeb‐Lundberg, F, Leurs, R, Lolait, SJ, Macewan, D, Maguire, JJ, May, JM, Mazella, J, Mcardle, CA, Mcdonnell, DP, Michel, MC, Miller, LJ, Mitolo, V, Monie, T, Monk, PN, Mouillac, B, Murphy, PM, Nahon, J‐L, Nerbonne, J, Nichols, CG, Norel, X, Oakley, R, Offermanns, S, Palmer, LG, Panaro, MA, Perez‐Reyes, E, Pertwee, RG, Pike, JW, Pin, JP, Pintor, S, Plant, LD, Poyner, DR, Prossnitz, ER, Pyne, S, Ren, D, Richer, JK, Rondard, P, Ross, RA, Sackin, H, Safi, R, Sanguinetti, MC, Sartorius, CA, Segaloff, DL, Sladek, FM, Stewart, G, Stoddart, LA, Striessnig, J, Summers, RJ, Takeda, Y, Tetel, M, Toll, L, Trimmer, JS, Tsai, M‐J, Tsai, SY, Tucker, S, Usdin, TB, Vilargada, J‐P, Vore, M, Ward, DT, Waxman, SG, Webb, P, Wei, AD, Weigel, N, Willars, GB, Winrow, C, Wong, SS, Wulff, H, Ye, RD, Young, M, and Zajac, J‐M
Subjects: Pharmacology, Summary information, business.industry, The Concise Guide to PHARMACOLOGY 2015/16, Medicine, Catalytic receptors, business, 3. Good health
Abstract: The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

17. The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis.

Author: Talamonti E, Davegardh J, Kalinovich A, van Beek SMM, Dehvari N, Halleskog C, Bokhari HM, Hutchinson DS, Ham S, Humphrys LJ, Dijon NC, Motso A, Sandstrom A, Zacharewicz E, Mutule I, Suna E, Spura J, Ditrychova K, Stoddart LA, Holliday ND, Wright SC, Lauschke VM, Nielsen S, Scheele C, Cheesman E, Hoeks J, Molenaar P, Summers RJ, Pelcman B, Yakala GK, and Bengtsson T
Subjects: Animals, Mice, Male, Rats, Obesity metabolism, Obesity drug therapy, Fatty Liver metabolism, Fatty Liver drug therapy, Thermogenesis drug effects, Adrenergic Agonists pharmacology, Adipose Tissue, Brown metabolism, Adipose Tissue, Brown drug effects, Muscle, Skeletal metabolism, Muscle, Skeletal drug effects, Mice, Inbred C57BL
Abstract: Objective: Simultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models., Methods: In the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective β-AR agonist isoprenaline across various rodent β-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis., Results: Exposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis., Conclusions: Our results demonstrate that ATR-127 is a highly effective, novel β2- and β3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TB, BP and ND own stocks in Atrogi AB. ET, AK, ND, SvB, CH, MHB, AS, BP and GY are employed by Atrogi AB. VML is co-founder, CEO and shareholder of HepaPredict AB., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Published: 2024
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18. The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.

Author: Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA, Abbracchio MP, Abraham G, Agoulnik A, Alexander W, Al-Hosaini K, Bäck M, Baker JG, Barnes NM, Bathgate R, Beaulieu JM, Beck-Sickinger AG, Behrens M, Bernstein KE, Bettler B, Birdsall NJM, Blaho V, Boulay F, Bousquet C, Bräuner-Osborne H, Burnstock G, Caló G, Castaño JP, Catt KJ, Ceruti S, Chazot P, Chiang N, Chini B, Chun J, Cianciulli A, Civelli O, Clapp LH, Couture R, Cox HM, Csaba Z, Dahlgren C, Dent G, Douglas SD, Dournaud P, Eguchi S, Escher E, Filardo EJ, Fong T, Fumagalli M, Gainetdinov RR, Garelja ML, de Gasparo M, Gerard C, Gershengorn M, Gobeil F, Goodfriend TL, Goudet C, Grätz L, Gregory KJ, Gundlach AL, Hamann J, Hanson J, Hauger RL, Hay DL, Heinemann A, Herr D, Hollenberg MD, Holliday ND, Horiuchi M, Hoyer D, Hunyady L, Husain A, IJzerman AP, Inagami T, Jacobson KA, Jensen RT, Jockers R, Jonnalagadda D, Karnik S, Kaupmann K, Kemp J, Kennedy C, Kihara Y, Kitazawa T, Kozielewicz P, Kreienkamp HJ, Kukkonen JP, Langenhan T, Larhammar D, Leach K, Lecca D, Lee JD, Leeman SE, Leprince J, Li XX, Lolait SJ, Lupp A, Macrae R, Maguire J, Malfacini D, Mazella J, McArdle CA, Melmed S, Michel MC, Miller LJ, Mitolo V, Mouillac B, Müller CE, Murphy PM, Nahon JL, Ngo T, Norel X, Nyimanu D, O'Carroll AM, Offermanns S, Panaro MA, Parmentier M, Pertwee RG, Pin JP, Prossnitz ER, Quinn M, Ramachandran R, Ray M, Reinscheid RK, Rondard P, Rovati GE, Ruzza C, Sanger GJ, Schöneberg T, Schulte G, Schulz S, Segaloff DL, Serhan CN, Singh KD, Smith CM, Stoddart LA, Sugimoto Y, Summers R, Tan VP, Thal D, Thomas WW, Timmermans PBMWM, Tirupula K, Toll L, Tulipano G, Unal H, Unger T, Valant C, Vanderheyden P, Vaudry D, Vaudry H, Vilardaga JP, Walker CS, Wang JM, Ward DT, Wester HJ, Willars GB, Williams TL, Woodruff TM, Yao C, and Ye RD
Subjects: Humans, Ligands, Ion Channels chemistry, Receptors, Cytoplasmic and Nuclear, Databases, Pharmaceutical, Receptors, G-Protein-Coupled
Abstract: The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)
Published: 2023
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19. Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor.

Author: Dekkers S, Caspar B, Goulding J, Kindon ND, Kilpatrick LE, Stoddart LA, Briddon SJ, Kellam B, Hill SJ, and Stocks MJ
Subjects: Ligands, Protein Binding, Chemokines metabolism, Chemokine CXCL12 metabolism, Receptors, CXCR4 metabolism, Fluorescent Dyes chemistry
Abstract: The C-X-C chemokine receptor type 4, or CXCR4, is a chemokine receptor found to promote cancer progression and metastasis of various cancer cell types. To investigate the pharmacology of this receptor, and to further elucidate its role in cancer, novel chemical tools are a necessity. In the present study, using classic medicinal chemistry approaches, small-molecule-based fluorescent probes were designed and synthesized based on previously reported small-molecule antagonists. Here, we report the development of three distinct chemical classes of fluorescent probes that show specific binding to the CXCR4 receptor in a novel fluorescence-based NanoBRET binding assay (p K D ranging 6.6-7.1). Due to their retained affinity at CXCR4, we furthermore report their use in competition binding experiments and confocal microscopy to investigate the pharmacology and cellular distribution of this receptor.
Published: 2023
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20. Optimization of Peptide Linker-Based Fluorescent Ligands for the Histamine H 1 Receptor.

Author: Kok ZY, Stoddart LA, Mistry SJ, Mocking TAM, Vischer HF, Leurs R, Hill SJ, Mistry SN, and Kellam B
Subjects: Fluorescent Dyes metabolism, Humans, Ligands, Molecular Docking Simulation, Peptides, Receptors, Histamine metabolism, Histamine, Receptors, Histamine H1 metabolism
Abstract: The histamine H 1 receptor (H 1 R) has recently been implicated in mediating cell proliferation and cancer progression; therefore, high-affinity H 1 R-selective fluorescent ligands are desirable tools for further investigation of this behavior in vitro and in vivo. We previously reported a H 1 R fluorescent ligand, bearing a peptide-linker, based on antagonist VUF13816 and sought to further explore structure-activity relationships (SARs) around the linker, orthostere, and fluorescent moieties. Here, we report a series of high-affinity H 1 R fluorescent ligands varying in peptide linker composition, orthosteric targeting moiety, and fluorophore. Incorporation of a boron-dipyrromethene (BODIPY) 630/650-based fluorophore conferred high binding affinity to our H 1 R fluorescent ligands, remarkably overriding the linker SAR observed in corresponding unlabeled congeners. Compound 31a , both potent and subtype-selective, enabled H 1 R visualization using confocal microscopy at a concentration of 10 nM. Molecular docking of 31a with the human H 1 R predicts that the optimized peptide linker makes interactions with key residues in the receptor.
Published: 2022
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21. Advances in the application of fluorescence correlation spectroscopy to study detergent purified and encapsulated membrane proteins.

Author: Stoddart LA, Goulding J, and Briddon SJ
Subjects: Fluorescence, Lipid Bilayers chemistry, Polystyrenes chemistry, Detergents, Membrane Proteins chemistry
Abstract: Fluorescence correlation spectroscopy (FCS) is a quantitative spectroscopy technique which could potentially increase throughput and sensitivity of screening for ligand, substrate and inhibitor binding to membrane proteins in solution. However, the purification of membrane proteins in their active forms is complex, as the lipid bilayer provides stability and its removal often causes the protein to become conformationally unstable. This has limited the application of biophysical techniques such as FCS to study the function of membrane proteins. The recent application of native extraction techniques such as styrene maleic acid lipid particles (SMALPs) has resolved this issue and FCS has emerged as a powerful option for studying proteins extracted in this way. This review will discuss the application of FCS to study purified membrane proteins in detergent micelles, nanodiscs and SMALPs and its potential to be used routinely in membrane protein drug discovery., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2022
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22. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.

Author: Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Southan C, Davies JA, Abbracchio MP, Alexander W, Al-Hosaini K, Bäck M, Barnes NM, Bathgate R, Beaulieu JM, Bernstein KE, Bettler B, Birdsall NJM, Blaho V, Boulay F, Bousquet C, Bräuner-Osborne H, Burnstock G, Caló G, Castaño JP, Catt KJ, Ceruti S, Chazot P, Chiang N, Chini B, Chun J, Cianciulli A, Civelli O, Clapp LH, Couture R, Csaba Z, Dahlgren C, Dent G, Singh KD, Douglas SD, Dournaud P, Eguchi S, Escher E, Filardo EJ, Fong T, Fumagalli M, Gainetdinov RR, Gasparo M, Gerard C, Gershengorn M, Gobeil F, Goodfriend TL, Goudet C, Gregory KJ, Gundlach AL, Hamann J, Hanson J, Hauger RL, Hay DL, Heinemann A, Hollenberg MD, Holliday ND, Horiuchi M, Hoyer D, Hunyady L, Husain A, IJzerman AP, Inagami T, Jacobson KA, Jensen RT, Jockers R, Jonnalagadda D, Karnik S, Kaupmann K, Kemp J, Kennedy C, Kihara Y, Kitazawa T, Kozielewicz P, Kreienkamp HJ, Kukkonen JP, Langenhan T, Leach K, Lecca D, Lee JD, Leeman SE, Leprince J, Li XX, Williams TL, Lolait SJ, Lupp A, Macrae R, Maguire J, Mazella J, McArdle CA, Melmed S, Michel MC, Miller LJ, Mitolo V, Mouillac B, Müller CE, Murphy P, Nahon JL, Ngo T, Norel X, Nyimanu D, O'Carroll AM, Offermanns S, Panaro MA, Parmentier M, Pertwee RG, Pin JP, Prossnitz ER, Quinn M, Ramachandran R, Ray M, Reinscheid RK, Rondard P, Rovati GE, Ruzza C, Sanger GJ, Schöneberg T, Schulte G, Schulz S, Segaloff DL, Serhan CN, Stoddart LA, Sugimoto Y, Summers R, Tan VP, Thal D, Thomas WW, Timmermans PBMWM, Tirupula K, Tulipano G, Unal H, Unger T, Valant C, Vanderheyden P, Vaudry D, Vaudry H, Vilardaga JP, Walker CS, Wang JM, Ward DT, Wester HJ, Willars GB, Woodruff TM, Yao C, and Ye RD
Subjects: Humans, Ion Channels, Ligands, Receptors, Cytoplasmic and Nuclear, Receptors, G-Protein-Coupled, Databases, Pharmaceutical, Pharmacology
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)
Published: 2021
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23. Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A 1 Receptor in Living Cells.

Author: Comeo E, Trinh P, Nguyen AT, Nowell CJ, Kindon ND, Soave M, Stoddart LA, White JM, Hill SJ, Kellam B, Halls ML, May LT, and Scammells PJ
Subjects: Adenosine A1 Receptor Antagonists metabolism, Bridged Bicyclo Compounds chemistry, Drug Design, Fluorescence Resonance Energy Transfer, Fluorescent Dyes metabolism, HEK293 Cells, Humans, Kinetics, Ligands, Octanes chemistry, Receptor, Adenosine A1 metabolism, Structure-Activity Relationship, Xanthine chemistry, Xanthine metabolism, Adenosine A1 Receptor Antagonists chemical synthesis, Fluorescent Dyes chemistry, Receptor, Adenosine A1 chemistry
Abstract: The adenosine A 1 receptor (A 1 AR) is a G-protein-coupled receptor (GPCR) that provides important therapeutic opportunities for a number of conditions including congestive heart failure, tachycardia, and neuropathic pain. The development of A 1 AR-selective fluorescent ligands will enhance our understanding of the subcellular mechanisms underlying A 1 AR pharmacology facilitating the development of more efficacious and selective therapies. Herein, we report the design, synthesis, and application of a novel series of A 1 AR-selective fluorescent probes based on 8-functionalized bicyclo[2.2.2]octylxanthine and 3-functionalized 8-(adamant-1-yl) xanthine scaffolds. These fluorescent conjugates allowed quantification of kinetic and equilibrium ligand binding parameters using NanoBRET and visualization of specific receptor distribution patterns in living cells by confocal imaging and total internal reflection fluorescence (TIRF) microscopy. As such, the novel A 1 AR-selective fluorescent antagonists described herein can be applied in conjunction with a series of fluorescence-based techniques to foster understanding of A 1 AR molecular pharmacology and signaling in living cells.
Published: 2021
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24. Efficient G protein coupling is not required for agonist-mediated internalization and membrane reorganization of the adenosine A 3 receptor.

Author: Stoddart LA, Kilpatrick LE, Corriden R, Kellam B, Briddon SJ, and Hill SJ
Subjects: Adenosine pharmacology, Animals, Arrestin metabolism, CHO Cells, Cricetulus, Gene Expression Regulation drug effects, Mutation, Protein Binding, Receptor, Adenosine A3 genetics, Adenosine analogs & derivatives, Adenosine A3 Receptor Agonists pharmacology, Boron Compounds pharmacology, GTP-Binding Proteins metabolism, Receptor, Adenosine A3 metabolism
Abstract: Organization of G protein-coupled receptors at the plasma membrane has been the focus of much recent attention. Advanced microscopy techniques have shown that these receptors can be localized to discrete microdomains and reorganization upon ligand activation is crucial in orchestrating their signaling. Here, we have compared the membrane organization and downstream signaling of a mutant (R108A, R3.50A) of the adenosine A 3 receptor (A 3 AR) to that of the wild-type receptor. Fluorescence Correlation Spectroscopy (FCS) studies with a fluorescent agonist (ABEA-X-BY630) demonstrated that both wild-type and mutant receptors bind agonist with high affinity but in subsequent downstream signaling assays the R108A mutation abolished agonist-mediated inhibition of cAMP production and ERK phosphorylation. In further FCS studies, both A 3 AR and A 3 AR R108A underwent similar agonist-induced increases in receptor density and molecular brightness which were accompanied by a decrease in membrane diffusion after agonist treatment. Using bimolecular fluorescence complementation, experiments showed that the R108A mutant retained the ability to recruit β-arrestin and these receptor/arrestin complexes displayed similar membrane diffusion and organization to that observed with wild-type receptors. These data demonstrate that effective G protein signaling is not a prerequisite for agonist-stimulated β-arrestin recruitment and membrane reorganization of the A 3 AR., (© 2021 Federation of American Societies for Experimental Biology.)
Published: 2021
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25. Detection of genome-edited and endogenously expressed G protein-coupled receptors.

Author: Soave M, Stoddart LA, White CW, Kilpatrick LE, Goulding J, Briddon SJ, and Hill SJ
Subjects: Gene Expression Regulation genetics, Humans, Ligands, Signal Transduction genetics, Drug Discovery, Gene Editing, Receptors, G-Protein-Coupled genetics
Abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and major targets for FDA-approved drugs. The ability to quantify GPCR expression and ligand binding characteristics in different cell types and tissues is therefore important for drug discovery. The advent of genome editing along with developments in fluorescent ligand design offers exciting new possibilities to probe GPCRs in their native environment. This review provides an overview of the recent technical advances employed to study the localisation and ligand binding characteristics of genome-edited and endogenously expressed GPCRs., (© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Published: 2021
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26. Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells.

Author: Stoddart LA, Kindon ND, Otun O, Harwood CR, Patera F, Veprintsev DB, Woolard J, Briddon SJ, Franks HA, Hill SJ, and Kellam B
Subjects: Affinity Labels, Drug Design, HEK293 Cells, Humans, Ligands, Receptor, Adenosine A2A metabolism, Fluorescent Dyes, Receptors, G-Protein-Coupled metabolism, Triazines, Triazoles
Abstract: To study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the receptor or the limitations of dissociable fluorescent ligands, here we describe rational design of a compound that covalently and selectively labels a GPCR in living cells with a fluorescent moiety. We designed a fluorescent antagonist, in which the linker incorporated between pharmacophore (ZM241385) and fluorophore (sulfo-cyanine5) is able to facilitate covalent linking of the fluorophore to the adenosine A 2A receptor. We pharmacologically and biochemically demonstrate irreversible fluorescent labelling without impeding access to the orthosteric binding site and demonstrate its use in endogenously expressing systems. This offers a non-invasive and selective approach to study function and localisation of native GPCRs.
Published: 2020
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27. Single molecule binding of a ligand to a G-protein-coupled receptor in real time using fluorescence correlation spectroscopy, rendered possible by nano-encapsulation in styrene maleic acid lipid particles.

Author: Grime RL, Goulding J, Uddin R, Stoddart LA, Hill SJ, Poyner DR, Briddon SJ, and Wheatley M
Subjects: Biomimetic Materials, Fluorescence, Humans, Membrane Lipids chemistry, Membrane Lipids metabolism, Protein Binding, Receptor, Adenosine A2A chemistry, Receptor, Adenosine A2A metabolism, Receptors, G-Protein-Coupled chemistry, Single Molecule Imaging, Spectrometry, Fluorescence, Ligands, Maleates chemistry, Receptors, G-Protein-Coupled metabolism, Styrene chemistry
Abstract: The fundamental importance of membrane proteins in cellular processes has driven a marked increase in the use of membrane mimetic approaches for studying and exploiting these proteins. Nano-encapsulation strategies which preserve the native lipid bilayer environment are particularly attractive. Consequently, the use of poly(styrene co-maleic acid) (SMA) has been widely adopted to solubilise proteins directly from cell membranes by spontaneously forming "SMA Lipid Particles" (SMALPs). G-protein-coupled receptors (GPCRs) are ubiquitous "chemical switches", are central to cell signalling throughout the evolutionary tree, form the largest family of membrane proteins in humans and are a major drug discovery target. GPCR-SMALPs that retain binding capability would be a versatile platform for a wide range of down-stream applications. Here, using the adenosine A2A receptor (A2AR) as an archetypical GPCR, we show for the first time the utility of fluorescence correlation spectroscopy (FCS) to characterise the binding capability of GPCRs following nano-encapsulation. Unbound fluorescent ligand CA200645 exhibited a monophasic autocorrelation curve (dwell time, τD = 68 ± 2 μs; diffusion coefficient, D = 287 ± 15 μm2 s-1). In the presence of A2AR-SMALP, bound ligand was also evident (τD = 625 ± 23 μs; D = 30 ± 4 μm2 s-1). Using a non-receptor control (ZipA-SMALP) plus competition binding confirmed that this slower component represented binding to the encapsulated A2AR. Consequently, the combination of GPCR-SMALP and FCS is an effective platform for the quantitative real-time characterisation of nano-encapsulated receptors, with single molecule sensitivity, that will have widespread utility for future exploitation of GPCR-SMALPs in general.
Published: 2020
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28. Subtype-Selective Fluorescent Ligands as Pharmacological Research Tools for the Human Adenosine A 2A Receptor.

Author: Comeo E, Kindon ND, Soave M, Stoddart LA, Kilpatrick LE, Scammells PJ, Hill SJ, and Kellam B
Subjects: Adenosine A2 Receptor Antagonists metabolism, Adenosine A2 Receptor Antagonists pharmacology, Drug Discovery, Fluorescent Dyes metabolism, Fluorescent Dyes pharmacology, HEK293 Cells, Humans, Ligands, Molecular Docking Simulation, Optical Imaging, Pyrimidines metabolism, Pyrimidines pharmacology, Receptor, Adenosine A2A metabolism, Triazoles metabolism, Triazoles pharmacology, Adenosine A2 Receptor Antagonists chemistry, Fluorescent Dyes chemistry, Pyrimidines chemistry, Receptor, Adenosine A2A analysis, Triazoles chemistry
Abstract: Among class A G protein-coupled receptors (GPCR), the human adenosine A 2A receptor (hA 2A AR) remains an attractive drug target. However, translation of A 2A AR ligands into the clinic has proved challenging and an improved understanding of A 2A AR pharmacology could promote development of more efficacious therapies. Subtype-selective fluorescent probes would allow detailed real-time pharmacological investigations both in vitro and in vivo. In the present study, two families of fluorescent probes were designed around the known hA 2A AR selective antagonist preladenant (SCH 420814). Both families of fluorescent antagonists retained affinity at the hA 2A AR, selectivity over all other adenosine receptor subtypes and allowed clear visualization of specific receptor localization through confocal imaging. Furthermore, the Alexa Fluor 647-labeled conjugate allowed measurement of ligand binding affinities of unlabeled hA 2A AR antagonists using a bioluminescence resonance energy transfer (NanoBRET) assay. The fluorescent ligands developed here can therefore be applied to a range of fluorescence-based techniques to further interrogate hA 2A AR pharmacology and signaling.
Published: 2020
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29. Fluorescent ligands: Bringing light to emerging GPCR paradigms.

Author: Soave M, Briddon SJ, Hill SJ, and Stoddart LA
Subjects: Fluorescent Dyes, Kinetics, Ligands, Receptors, G-Protein-Coupled, Signal Transduction
Abstract: In recent years, several novel aspects of GPCR pharmacology have been described, which are thought to play a role in determining the in vivo efficacy of a compound. Fluorescent ligands have been used to study many of these, which have also required the development of new experimental approaches. Fluorescent ligands offer the potential to use the same fluorescent probe to perform a broad range of experiments, from single-molecule microscopy to in vivo BRET. This review provides an overview of the in vitro use of fluorescent ligands in further understanding emerging pharmacological paradigms within the GPCR field, including ligand-binding kinetics, allosterism and intracellular signalling, along with the use of fluorescent ligands to study physiologically relevant therapeutic agents., (© 2019 The British Pharmacological Society.)
Published: 2020
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30. Application of Fluorescent Purinoceptor Antagonists for Bioluminescence Resonance Energy Transfer Assays and Fluorescent Microscopy.

Author: Soave M, Goulding J, Markus R, Hill SJ, and Stoddart LA
Subjects: Fluorescence, HEK293 Cells, Humans, Luciferases metabolism, Protein Binding, Protein Multimerization, Purinergic P1 Receptor Agonists chemistry, Receptor, Adenosine A3 chemistry, Receptors, Purinergic P1 chemistry, Signal Transduction, Bioluminescence Resonance Energy Transfer Techniques methods, Microscopy, Fluorescence methods, Purinergic P1 Receptor Agonists metabolism, Receptor, Adenosine A3 metabolism, Receptors, Purinergic P1 metabolism
Abstract: Fluorescent antagonists offer the ability to interrogate G protein-coupled receptor pharmacology. With resonance energy transfer techniques, fluorescent antagonists can be implemented to monitor receptor-ligand interactions using assays originally designed for radiolabeled probes. The fluorescent nature of these antagonists also enables the localization and distribution of the receptors to be visualized in living cells. Here, we describe the generation of modified purinergic receptors with the NanoLuc luciferase or SNAP-tag, using the P1 adenosine A 3 receptor as an example. We also describe the procedure of characterizing a novel fluorescent purinergic antagonist using ligand-mediated bioluminescence resonance energy transfer assays and confocal microscopy.
Published: 2020
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31. A live cell NanoBRET binding assay allows the study of ligand-binding kinetics to the adenosine A 3 receptor.

Author: Bouzo-Lorenzo M, Stoddart LA, Xia L, IJzerman AP, Heitman LH, Briddon SJ, and Hill SJ
Subjects: HEK293 Cells, Humans, Kinetics, Adenosine A3 Receptor Antagonists pharmacokinetics, Fluorescence Resonance Energy Transfer methods, Luminescent Measurements, Receptor, Adenosine A3 metabolism
Abstract: There is a growing interest in understanding the binding kinetics of compounds that bind to G protein-coupled receptors prior to progressing a lead compound into clinical trials. The widely expressed adenosine A 3 receptor (A 3 AR) has been implicated in a range of diseases including immune conditions, and compounds that aim to selectively target this receptor are currently under development for arthritis. Kinetic studies at the A 3 AR have been performed using a radiolabelled antagonist, but due to the kinetics of this probe, they have been carried out at 10 °C in membrane preparations. In this study, we have developed a live cell NanoBRET ligand binding assay using fluorescent A 3 AR antagonists to measure kinetic parameters of labelled and unlabelled compounds at the A 3 AR at physiological temperatures. The kinetic profiles of four fluorescent antagonists were determined in kinetic association assays, and it was found that XAC-ser-tyr-X-BY630 had the longest residence time (RT = 288 ± 62 min) at the A 3 AR. The association and dissociation rate constants of three antagonists PSB-11, compound 5, and LUF7565 were also determined using two fluorescent ligands (XAC-ser-tyr-X-BY630 or AV039, RT = 6.8 ± 0.8 min) as the labelled probe and compared to those obtained using a radiolabelled antagonist ([ 3 H]PSB-11, RT = 44.6 ± 3.9 min). There was close agreement in the kinetic parameters measured with AV039 and [ 3 H]PSB-11 but significant differences to those obtained using XAC-S-ser-S-tyr-X-BY630. These data indicate that selecting a probe with the appropriate kinetics is important to accurately determine the kinetics of unlabelled ligands with markedly different kinetic profiles.
Published: 2019
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32. Probe dependency in the determination of ligand binding kinetics at a prototypical G protein-coupled receptor.

Author: Bosma R, Stoddart LA, Georgi V, Bouzo-Lorenzo M, Bushby N, Inkoom L, Waring MJ, Briddon SJ, Vischer HF, Sheppard RJ, Fernández-Montalván A, Hill SJ, and Leurs R
Subjects: Cetirizine chemistry, Cetirizine pharmacokinetics, Datasets as Topic, Fluorescence Resonance Energy Transfer methods, Fluorescent Dyes chemistry, Fluorescent Dyes pharmacokinetics, HEK293 Cells, Histamine H1 Antagonists chemistry, Humans, Ligands, Molecular Probes pharmacokinetics, Olopatadine Hydrochloride chemistry, Olopatadine Hydrochloride pharmacokinetics, Protein Binding, Pyrilamine chemistry, Pyrilamine pharmacokinetics, Tritium, Binding, Competitive, Histamine H1 Antagonists pharmacokinetics, Molecular Probes chemistry, Radioligand Assay methods, Receptors, Histamine H1 metabolism
Abstract: Drug-target binding kinetics are suggested to be important parameters for the prediction of in vivo drug-efficacy. For G protein-coupled receptors (GPCRs), the binding kinetics of ligands are typically determined using association binding experiments in competition with radiolabelled probes, followed by analysis with the widely used competitive binding kinetics theory developed by Motulsky and Mahan. Despite this, the influence of the radioligand binding kinetics on the kinetic parameters derived for the ligands tested is often overlooked. To address this, binding rate constants for a series of histamine H 1 receptor (H 1 R) antagonists were determined using radioligands with either slow (low k off ) or fast (high k off ) dissociation characteristics. A correlation was observed between the probe-specific datasets for the kinetic binding affinities, association rate constants and dissociation rate constants. However, the magnitude and accuracy of the binding rate constant-values was highly dependent on the used radioligand probe. Further analysis using recently developed fluorescent binding methods corroborates the finding that the Motulsky-Mahan methodology is limited by the employed assay conditions. The presented data suggest that kinetic parameters of GPCR ligands depend largely on the characteristics of the probe used and results should therefore be viewed within the experimental context and limitations of the applied methodology.
Published: 2019
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33. Binding kinetics of ligands acting at GPCRs.

Author: Sykes DA, Stoddart LA, Kilpatrick LE, and Hill SJ
Subjects: Allosteric Regulation, Cell Membrane metabolism, Humans, Kinetics, Ligands, Models, Molecular, Protein Binding, Receptors, G-Protein-Coupled chemistry, Receptors, G-Protein-Coupled metabolism
Abstract: The influence of drug-receptor binding kinetics has often been overlooked during the development of new therapeutics that target G protein-coupled receptors (GPCRs). Over the last decade there has been a growing understanding that an in-depth knowledge of binding kinetics at GPCRs is required to successfully target this class of proteins. Ligand binding to a GPCR is often not a simple single step process with ligand freely diffusing in solution. This review will discuss the experiments and equations that are commonly used to measure binding kinetics and how factors such as allosteric regulation, rebinding and ligand interaction with the plasma membrane may influence these measurements. We will then consider the molecular characteristics of a ligand and if these can be linked to association and dissociation rates., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2019
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34. Correction to Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y 2 Receptor Based on AR-C118925.

Author: Conroy S, Kindon ND, Glenn J, Stoddart LA, Lewis RJ, Hill SJ, Kellam B, and Stocks MJ
Published: 2018
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35. Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y 2 Receptor Based on AR-C118925.

Author: Conroy S, Kindon ND, Glenn J, Stoddart LA, Lewis RJ, Hill SJ, Kellam B, and Stocks MJ
Subjects: Astrocytoma metabolism, Cell Line, Dibenzocycloheptenes chemistry, Humans, Ligands, Microscopy, Confocal, Molecular Probes, Protein Binding, Pyrimidinones chemistry, Recombinant Proteins chemistry, Structure-Activity Relationship, Dibenzocycloheptenes pharmacology, Fluorescent Dyes chemical synthesis, Fluorescent Dyes pharmacology, Purinergic P2 Receptor Antagonists chemical synthesis, Purinergic P2 Receptor Antagonists pharmacology, Pyrimidinones pharmacology, Receptors, Purinergic P2Y2 drug effects
Abstract: The human P2Y 2 receptor ( hP2Y 2 R) is a G-protein-coupled receptor that shows promise as a therapeutic target for many important conditions, including for antimetastatic cancer and more recently for idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y 2 R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y 2 R antagonists, based on the known, non-nucleotide hP2Y 2 R antagonist AR-C118925 (1), leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores. One of these conjugates, 98, displayed micromolar affinity for hP2Y 2 R (p K d = 6.32 ± 0.10, n = 17) in a bioluminescence-energy-transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing untagged hP2Y 2 R. These properties make 98 one of the first tools for studying hP2Y 2 R distribution and organization.
Published: 2018
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36. NanoBRET Approaches to Study Ligand Binding to GPCRs and RTKs.

Author: Stoddart LA, Kilpatrick LE, and Hill SJ
Subjects: Animals, Humans, Ligands, Protein Binding, Receptor Protein-Tyrosine Kinases metabolism, Receptors, G-Protein-Coupled metabolism, Bioluminescence Resonance Energy Transfer Techniques methods, Receptor Protein-Tyrosine Kinases chemistry, Receptors, G-Protein-Coupled chemistry, Single Molecule Imaging methods
Abstract: Recent advances in the development of fluorescent ligands for G-protein-coupled receptors (GPCRs) and receptor tyrosine kinase receptors (RTKs) have facilitated the study of these receptors in living cells. A limitation of these ligands is potential uptake into cells and increased nonspecific binding. However, this can largely be overcome by using proximity approaches, such as bioluminescence resonance energy transfer (BRET), which localise the signal (within 10nm) to the specific receptor target. The recent engineering of NanoLuc has resulted in a luciferase variant that is smaller and significantly brighter (up to tenfold) than existing variants. Here, we review the use of BRET from N-terminal NanoLuc-tagged GPCRs or a RTK to a receptor-bound fluorescent ligand to provide quantitative pharmacology of ligand-receptor interactions in living cells in real time., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
Published: 2018
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37. Development of novel fluorescent histamine H 1 -receptor antagonists to study ligand-binding kinetics in living cells.

Author: Stoddart LA, Vernall AJ, Bouzo-Lorenzo M, Bosma R, Kooistra AJ, de Graaf C, Vischer HF, Leurs R, Briddon SJ, Kellam B, and Hill SJ
Subjects: Fluorescence Resonance Energy Transfer, HEK293 Cells, Humans, Kinetics, Microscopy, Confocal, Protein Binding, Cytological Techniques methods, Fluorescent Dyes metabolism, Histamine H1 Antagonists metabolism
Abstract: The histamine H 1 -receptor (H 1 R) is an important mediator of allergy and inflammation. H 1 R antagonists have particular clinical utility in allergic rhinitis and urticaria. Here we have developed six novel fluorescent probes for this receptor that are very effective for high resolution confocal imaging, alongside bioluminescence resonance energy transfer approaches to monitor H 1 R ligand binding kinetics in living cells. The latter technology exploits the opportunities provided by the recently described bright bioluminescent protein NanoLuc when it is fused to the N-terminus of a receptor. Two different pharmacophores (mepyramine or the fragment VUF13816) were used to generate fluorescent H 1 R antagonists conjugated via peptide linkers to the fluorophore BODIPY630/650. Kinetic properties of the probes showed wide variation, with the VUF13816 analogues having much longer H 1 R residence times relative to their mepyramine-based counterparts. The kinetics of these fluorescent ligands could also be monitored in membrane preparations providing new opportunities for future drug discovery applications.
Published: 2018
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38. A Non-imaging High Throughput Approach to Chemical Library Screening at the Unmodified Adenosine-A 3 Receptor in Living Cells.

Author: Arruda MA, Stoddart LA, Gherbi K, Briddon SJ, Kellam B, and Hill SJ
Abstract: Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the binding of fluorescent ligands to the human adenosine-A 3 receptor (A 3 AR; CA200645 and AV039), stably expressed in CHO-K1 cells. To verify that this method was suitable for the study of other GPCRs, assays at the human adenosine-A 1 receptor, and β 1 and β 2 adrenoceptors (β 1 AR and β 2 AR; BODIPY-TMR-CGP-12177) were also carried out. Affinity values determined for the binding of the fluorescent ligands CA200645 and AV039 to A 3 AR for a range of classical adenosine receptor antagonists were consistent with A 3 AR pharmacology and correlated well ( R 2 = 0.94) with equivalent data obtained using a confocal imaging plate reader (ImageXpress Ultra). The binding of BODIPY-TMR-CGP-12177 to the β 1 AR was potently inhibited by low concentrations of the β 1 -selective antagonist CGP 20712A (pK i 9.68) but not by the β 2 -selective antagonist ICI 118551(pK i 7.40). Furthermore, in experiments conducted in CHO K1 cells expressing the β 2 AR this affinity order was reversed with ICI 118551 showing the highest affinity (pK i 8.73) and CGP20712A (pK i 5.68) the lowest affinity. To determine whether the faster data acquisition of the non-imaging plate reader (~3 min per 96-well plate) was suitable for high throughput screening (HTS), we screened the LOPAC library for inhibitors of the binding of CA200645 to the A 3 AR. From the initial 1,263 compounds evaluated, 67 hits (defined as those that inhibited the total binding of 25 nM CA200645 by ≥40%) were identified. All compounds within the library that had medium to high affinity for the A 3 AR (pK i ≥6) were successfully identified. We found three novel compounds in the library that displayed unexpected sub-micromolar affinity for the A 3 AR. These were K114 (pK i 6.43), retinoic acid p -hydroxyanilide (pK i 6.13) and SU 6556 (pK i 6.17). Molecular docking of these latter three LOPAC library members provided a plausible set of binding poses within the vicinity of the established orthosteric A 3 AR binding pocket. A plate reader based library screening using an untagged receptor is therefore possible using fluorescent ligand opening the possibility of its use in compound screening at natively expressed receptors.
Published: 2017
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39. Kinetics for Drug Discovery: an industry-driven effort to target drug residence time.

Author: Schuetz DA, de Witte WEA, Wong YC, Knasmueller B, Richter L, Kokh DB, Sadiq SK, Bosma R, Nederpelt I, Heitman LH, Segala E, Amaral M, Guo D, Andres D, Georgi V, Stoddart LA, Hill S, Cooke RM, De Graaf C, Leurs R, Frech M, Wade RC, de Lange ECM, IJzerman AP, Müller-Fahrnow A, and Ecker GF
Subjects: Animals, Drug Industry, Humans, Kinetics, Pharmacokinetics, Drug Discovery, Pharmaceutical Preparations metabolism
Abstract: A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership., (Copyright © 2017. Published by Elsevier Ltd.)
Published: 2017
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40. Design and Elaboration of a Tractable Tricyclic Scaffold To Synthesize Druglike Inhibitors of Dipeptidyl Peptidase-4 (DPP-4), Antagonists of the C-C Chemokine Receptor Type 5 (CCR5), and Highly Potent and Selective Phosphoinositol-3 Kinase δ (PI3Kδ) Inhibitors.

Author: Schwehm C, Kellam B, Garces AE, Hill SJ, Kindon ND, Bradshaw TD, Li J, Macdonald SJ, Rowedder JE, Stoddart LA, and Stocks MJ
Subjects: Class Ia Phosphatidylinositol 3-Kinase metabolism, Dipeptidyl Peptidase 4 metabolism, Drug Design, Humans, Molecular Docking Simulation, Protein Subunits antagonists & inhibitors, Protein Subunits metabolism, Receptors, CCR5 metabolism, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, CCR5 Receptor Antagonists chemistry, CCR5 Receptor Antagonists pharmacology, Dipeptidyl-Peptidase IV Inhibitors chemistry, Dipeptidyl-Peptidase IV Inhibitors pharmacology, Phosphoinositide-3 Kinase Inhibitors, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology
Abstract: A novel molecular scaffold has been synthesized, and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies, we have shown use of the tricyclic scaffold to synthesize potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs.
Published: 2017
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41. Fluorescence- and bioluminescence-based approaches to study GPCR ligand binding.

Author: Stoddart LA, White CW, Nguyen K, Hill SJ, and Pfleger KD
Subjects: Binding Sites drug effects, Fluorescent Dyes chemistry, Humans, Ligands, Receptors, G-Protein-Coupled metabolism, Fluorescence, Fluorescence Resonance Energy Transfer, Fluorescent Dyes pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors
Abstract: Ligand binding is a vital component of any pharmacologist's toolbox and allows the detailed investigation of how a molecule binds to its receptor. These studies enable the experimental determination of binding affinity of labelled and unlabelled compounds through kinetic, saturation (Kd ) and competition (Ki ) binding assays. Traditionally, these studies have used molecules labelled with radioisotopes; however, more recently, fluorescent ligands have been developed for this purpose. This review will briefly cover receptor ligand binding theory and then discuss the use of fluorescent ligands with some of the different technologies currently employed to examine ligand binding. Fluorescent ligands can be used for direct measurement of receptor-associated fluorescence using confocal microscopy and flow cytometry as well as in assays such as fluorescence polarization, where ligand binding is monitored by changes in the free rotation when a fluorescent ligand is bound to a receptor. Additionally, fluorescent ligands can act as donors or acceptors for fluorescence resonance energy transfer (FRET) with the development of assays based on FRET and time-resolved FRET (TR-FRET). Finally, we have recently developed a novel bioluminescence resonance energy transfer (BRET) ligand binding assay utilizing a small (19 kDa), super-bright luciferase subunit (NanoLuc) from a deep sea shrimp. In combination with fluorescent ligands, measurement of RET now provides an array of methodologies to study ligand binding. While each method has its own advantages and drawbacks, binding studies using fluorescent ligands are now a viable alternative to the use of radioligands. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc., (© 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Published: 2016
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42. Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the human β 1 -adrenoceptor expressed in HEK-293 cells.

Author: Soave M, Stoddart LA, Brown A, Woolard J, and Hill SJ
Abstract: Previous research has indicated that allosteric interactions across the dimer interface of β 1 -adrenoceptors may be responsible for a secondary low affinity binding conformation. Here we have investigated the potential for probe dependence, in the determination of antagonist pK i values at the human β 1 -adenoceptor, which may result from such allosterism interactions. Three fluorescent β 1 -adrenoceptor ligands were used to investigate this using bioluminescence energy transfer (BRET) between the receptor-bound fluorescent ligand and the N-terminal NanoLuc tag of a human β 1 -adrenoceptor expressed in HEK 293 cells (NanoBRET). This proximity assay showed high-affinity-specific binding to the NanoLuc- β 1 -adrenoceptor with each of the three fluorescent ligands yielding K D values of 87.1 ± 10 nmol/L ( n = 8), 38.1 ± 12 nmol/L ( n = 7), 13.4 ± 2 nmol/L ( n = 14) for propranolol-Peg8-BY630, propranolol- β (Ala-Ala)-BY630 and CGP-12177-TMR, respectively. Parallel radioligand-binding studies with 3 H-CGP12177 and TIRF microscopy, to monitor NanoLuc bioluminescence, confirmed a high cell surface expression of the NanoLuc- β 1 -adrenoceptor in HEK 293 cells (circa 1500 fmol.mg protein -1 ). Following a 1 h incubation with fluorescent ligands and β 1 -adrenoceptor competing antagonists, there were significant differences ( P < 0.001) in the pK i values obtained for CGP20712a and CGP 12177 with the different fluorescent ligands and 3 H-CGP 12177. However, increasing the incubation time to 2 h removed these significant differences. The data obtained show that the NanoBRET assay can be applied successfully to study ligand-receptor interactions at the human β 1 -adrenoceptor. However, the study also emphasizes the importance of ensuring that both the fluorescent and competing ligands are in true equilibrium before interpretations regarding probe dependence can be made.
Published: 2016
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43. Synthesis, Biological Evaluation, and Utility of Fluorescent Ligands Targeting the μ-Opioid Receptor.

Author: Schembri LS, Stoddart LA, Briddon SJ, Kellam B, Canals M, Graham B, and Scammells PJ
Subjects: Animals, Binding, Competitive, Buprenorphine pharmacology, CHO Cells, Cricetulus, Fluorescent Dyes pharmacology, HEK293 Cells, Humans, Ligands, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Phosphorylation, Radioligand Assay, Receptors, Opioid, mu antagonists & inhibitors, Stereoisomerism, Structure-Activity Relationship, Buprenorphine analogs & derivatives, Buprenorphine chemistry, Fluorescent Dyes chemistry, Receptors, Opioid, mu metabolism
Abstract: Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology.
Published: 2015
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44. Fragment-Based Discovery of Subtype-Selective Adenosine Receptor Ligands from Homology Models.

Author: Ranganathan A, Stoddart LA, Hill SJ, and Carlsson J
Subjects: Adenosine A1 Receptor Antagonists chemistry, Adenosine A1 Receptor Antagonists pharmacology, Adenosine A3 Receptor Antagonists pharmacology, Animals, Binding, Competitive, CHO Cells, Computer Simulation, Cricetulus, High-Throughput Screening Assays, Humans, Ligands, Molecular Docking Simulation, Pyrimidinones pharmacology, Receptor, Adenosine A1 chemistry, Receptor, Adenosine A1 metabolism, Receptor, Adenosine A3 metabolism, Sequence Homology, Amino Acid, Small Molecule Libraries, Structure-Activity Relationship, Thiazoles pharmacology, Thiophenes pharmacology, Adenosine A3 Receptor Antagonists chemistry, Pyrimidinones chemistry, Receptor, Adenosine A3 chemistry, Thiazoles chemistry, Thiophenes chemistry
Abstract: Fragment-based lead discovery (FBLD) holds great promise for drug discovery, but applications to G protein-coupled receptors (GPCRs) have been limited by a lack of sensitive screening techniques and scarce structural information. If virtual screening against homology models of GPCRs could be used to identify fragment ligands, FBLD could be extended to numerous important drug targets and contribute to efficient lead generation. Access to models of multiple receptors may further enable the discovery of fragments that bind specifically to the desired target. To investigate these questions, we used molecular docking to screen >500 000 fragments against homology models of the A3 and A1 adenosine receptors (ARs) with the goal to discover A3AR-selective ligands. Twenty-one fragments with predicted A3AR-specific binding were evaluated in live-cell fluorescence-based assays; of eight verified ligands, six displayed A3/A1 selectivity, and three of these had high affinities ranging from 0.1 to 1.3 μM. Subsequently, structure-guided fragment-to-lead optimization led to the identification of a >100-fold-selective antagonist with nanomolar affinity from commercial libraries. These results highlight that molecular docking screening can guide fragment-based discovery of selective ligands even if the structures of both the target and antitarget receptors are unknown. The same approach can be readily extended to a large number of pharmaceutically important targets.
Published: 2015
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45. Direct visualisation of internalization of the adenosine A3 receptor and localization with arrestin3 using a fluorescent agonist.

Author: Stoddart LA, Vernall AJ, Briddon SJ, Kellam B, and Hill SJ
Subjects: Adenosine analogs & derivatives, Adenosine pharmacology, Adenosine A3 Receptor Agonists pharmacology, Adenosine-5'-(N-ethylcarboxamide) pharmacology, Animals, Arrestins genetics, Boron Compounds pharmacology, CHO Cells, Colforsin pharmacology, Cricetulus, Dose-Response Relationship, Drug, Fluorescent Dyes pharmacokinetics, Gene Expression drug effects, Ligands, Luminescent Proteins genetics, Luminescent Proteins metabolism, Microscopy, Confocal, Molecular Structure, Protein Transport physiology, Receptor, Adenosine A3 genetics, Time Factors, Transfection, Arrestins metabolism, Fluorescent Dyes chemistry, Receptor, Adenosine A3 metabolism
Abstract: Fluorescence based probes provide a novel way to study the dynamic internalization process of G protein-coupled receptors (GPCRs). Recent advances in the rational design of fluorescent ligands for GPCRs have been used here to generate new fluorescent agonists containing tripeptide linkers for the adenosine A3 receptor. The fluorescent agonist BY630-X-(D)-A-(D)-A-G-ABEA was found to be a highly potent agonist at the adenosine A3 receptor in both reporter gene (pEC50 = 8.48 ± 0.09) and internalization assays (pEC50 = 7.47 ± 0.11). Confocal imaging studies showed that BY630-X-(D)-A-(D)-A-G-ABEA was internalized with A3 linked to yellow fluorescent protein, which was blocked by the competitive antagonist MRS1220. Internalization of untagged adenosine A3 could also be visualized with BY630-X-(D)-A-(D)-A-G-ABEA treatment. Further, BY630-X-(D)-A-(D)-A-G-ABEA stimulated the formation of receptor-arrestin3 complexes and was found to localize with these intracellular complexes. This highly potent agonist with excellent imaging properties should be a valuable tool to study receptor internalization. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2015
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46. Probing the pharmacology of G protein-coupled receptors with fluorescent ligands.

Author: Stoddart LA, Kilpatrick LE, Briddon SJ, and Hill SJ
Subjects: Animals, Humans, Ligands, Radioligand Assay, Fluorescent Dyes chemistry, Fluorescent Dyes pharmacokinetics, Receptors, G-Protein-Coupled metabolism
Abstract: G protein-coupled receptors control a wide range of physiological processes and are the target for many clinically used drugs. Understanding the way in which receptors bind agonists and antagonists, their organisation in the membrane and their regulation after agonist binding are important properties which are key to developing new drugs. One way to achieve this knowledge is through the use of fluorescent ligands, which have been used to study the expression and function of receptors in endogenously expressing systems. Fluorescent ligands with appropriate imaging properties can be used in conjunction with confocal microscopy to investigate the regulation of receptors after activation. Alternatively, through the use of single molecule microscopy, they can probe the spatial organisation of receptors within the membrane. This review focuses on the techniques in which fluorescent ligands have been used and the novel aspects of G protein-coupled receptor pharmacology which have been uncovered. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2015
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47. Application of BRET to monitor ligand binding to GPCRs.

Author: Stoddart LA, Johnstone EKM, Wheal AJ, Goulding J, Robers MB, Machleidt T, Wood KV, Hill SJ, and Pfleger KDG
Subjects: Fluorescence, HEK293 Cells, Humans, Ligands, Receptors, Adrenergic, beta-2 metabolism, Bioluminescence Resonance Energy Transfer Techniques methods, Receptors, G-Protein-Coupled metabolism
Abstract: Bioluminescence resonance energy transfer (BRET) is a well-established method for investigating protein-protein interactions. Here we present a BRET approach to monitor ligand binding to G protein-coupled receptors (GPCRs) on the surface of living cells made possible by the use of fluorescent ligands in combination with a bioluminescent protein (NanoLuc) that can be readily expressed on the N terminus of GPCRs.
Published: 2015
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48. Effect of a toggle switch mutation in TM6 of the human adenosine A₃ receptor on Gi protein-dependent signalling and Gi-independent receptor internalization.

Author: Stoddart LA, Kellam B, Briddon SJ, and Hill SJ
Subjects: Adenosine analogs & derivatives, Adenosine pharmacology, Adenosine-5'-(N-ethylcarboxamide) pharmacology, Animals, Arrestins metabolism, CHO Cells, Cricetulus, Cyclic AMP metabolism, Humans, MAP Kinase Signaling System drug effects, Mutation, Protein Structure, Tertiary, Signal Transduction, beta-Arrestins, GTP-Binding Proteins metabolism, Purinergic P1 Receptor Agonists pharmacology, Receptor, Adenosine A3 genetics, Receptor, Adenosine A3 metabolism
Abstract: Background and Purpose: The highly conserved tryptophan (W6.48) in transmembrane domain 6 of GPCRs has been shown to play a central role in forming an active conformation in response to agonist binding. We set out to characterize the effect of this mutation on the efficacy of two agonists at multiple signalling pathways downstream of the adenosine A₃ receptor., Experimental Approach: Residue W6.48 in the human adenosine A₃ receptor fused to yellow fluorescent protein was mutated to phenylalanine and expressed in CHO-K1 cells containing a cAMP response element reporter gene. The effects on agonist-mediated receptor internalization were monitored by automated confocal microscopy and image analysis. Further experiments were carried out to investigate agonist-mediated ERK1/2 phosphorylation, inhibition of [(3)H]-cAMP accumulation and β-arrestin2 binding., Key Results: NECA was able to stimulate agonist-mediated internalization of the W6.48F mutant receptor, while the agonist HEMADO was inactive. Investigation of other downstream signalling pathways indicated that G-protein coupling was impaired for both agonists tested. Mutation of W6.48F therefore resulted in differential effects on agonist efficacy, and introduced signalling pathway bias for HEMADO at the adenosine A3 receptor., Conclusions and Implications: Investigation of the pharmacology of the W6.48F mutant of the adenosine A₃ receptor confirms that this region is important in forming the active conformation of the receptor for stimulating a number of different signalling pathways and that mutations in this residue can lead to changes in agonist efficacy and signalling bias., (© 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)
Published: 2014
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49. The Concise Guide to PHARMACOLOGY 2013/14: overview.

Author: Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, McGrath JC, Catterall WA, Spedding M, Peters JA, Harmar AJ, Abul-Hasn N, Anderson CM, Anderson CM, Araiksinen MS, Arita M, Arthofer E, Barker EL, Barratt C, Barnes NM, Bathgate R, Beart PM, Belelli D, Bennett AJ, Birdsall NJ, Boison D, Bonner TI, Brailsford L, Bröer S, Brown P, Calo G, Carter WG, Catterall WA, Chan SL, Chao MV, Chiang N, Christopoulos A, Chun JJ, Cidlowski J, Clapham DE, Cockcroft S, Connor MA, Cox HM, Cuthbert A, Dautzenberg FM, Davenport AP, Dawson PA, Dent G, Dijksterhuis JP, Dollery CT, Dolphin AC, Donowitz M, Dubocovich ML, Eiden L, Eidne K, Evans BA, Fabbro D, Fahlke C, Farndale R, Fitzgerald GA, Fong TM, Fowler CJ, Fry JR, Funk CD, Futerman AH, Ganapathy V, Gaisnier B, Gershengorn MA, Goldin A, Goldman ID, Gundlach AL, Hagenbuch B, Hales TG, Hammond JR, Hamon M, Hancox JC, Hauger RL, Hay DL, Hobbs AJ, Hollenberg MD, Holliday ND, Hoyer D, Hynes NA, Inui KI, Ishii S, Jacobson KA, Jarvis GE, Jarvis MF, Jensen R, Jones CE, Jones RL, Kaibuchi K, Kanai Y, Kennedy C, Kerr ID, Khan AA, Klienz MJ, Kukkonen JP, Lapoint JY, Leurs R, Lingueglia E, Lippiat J, Lolait SJ, Lummis SC, Lynch JW, MacEwan D, Maguire JJ, Marshall IL, May JM, McArdle CA, McGrath JC, Michel MC, Millar NS, Miller LJ, Mitolo V, Monk PN, Moore PK, Moorhouse AJ, Mouillac B, Murphy PM, Neubig RR, Neumaier J, Niesler B, Obaidat A, Offermanns S, Ohlstein E, Panaro MA, Parsons S, Pwrtwee RG, Petersen J, Pin JP, Poyner DR, Prigent S, Prossnitz ER, Pyne NJ, Pyne S, Quigley JG, Ramachandran R, Richelson EL, Roberts RE, Roskoski R, Ross RA, Roth M, Rudnick G, Ryan RM, Said SI, Schild L, Sanger GJ, Scholich K, Schousboe A, Schulte G, Schulz S, Serhan CN, Sexton PM, Sibley DR, Siegel JM, Singh G, Sitsapesan R, Smart TG, Smith DM, Soga T, Stahl A, Stewart G, Stoddart LA, Summers RJ, Thorens B, Thwaites DT, Toll L, Traynor JR, Usdin TB, Vandenberg RJ, Villalon C, Vore M, Waldman SA, Ward DT, Willars GB, Wonnacott SJ, Wright E, Ye RD, Yonezawa A, and Zimmermann M
Subjects: Humans, Ligands, Pharmaceutical Preparations chemistry, Databases, Pharmaceutical, Molecular Targeted Therapy, Pharmacology
Abstract: The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates., (Copyright © 2013 The British Pharmacological Society.)
Published: 2013
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50. Conversion of a non-selective adenosine receptor antagonist into A3-selective high affinity fluorescent probes using peptide-based linkers.

Author: Vernall AJ, Stoddart LA, Briddon SJ, Ng HW, Laughton CA, Doughty SW, Hill SJ, and Kellam B
Subjects: Animals, CHO Cells, Cricetulus, Fluorescent Dyes chemical synthesis, Humans, Models, Molecular, Molecular Structure, Fluorescent Dyes chemistry, Peptides chemistry, Purinergic P1 Receptor Antagonists chemistry
Abstract: Advances in fluorescence-based imaging technologies have helped propel the study of real-time biological readouts and analysis across many different areas. In particular the use of fluorescent ligands as chemical tools to study proteins such as G protein-coupled receptors (GPCRs) has received ongoing interest. Methods to improve the efficient chemical synthesis of fluorescent ligands remain of paramount importance to ensure this area of bioanalysis continues to advance. Here we report conversion of the non-selective GPCR adenosine receptor antagonist Xanthine Amine Congener into higher affinity and more receptor subtype-selective fluorescent antagonists. This was achieved through insertion and optimisation of a dipeptide linker between the adenosine receptor pharmacophore and the fluorophore. Fluorescent probe 27 containing BODIPY 630/650 (pK(D) = 9.12 ± 0.05 [hA3AR]), and BODIPY FL-containing 28 (pK(D) = 7.96 ± 0.09 [hA3AR]) demonstrated clear, displaceable membrane binding using fluorescent confocal microscopy. From in silico analysis of the docked ligand-receptor complexes of 27, we suggest regions of molecular interaction that could account for the observed selectivity of these peptide-linker based fluorescent conjugates. This general approach of converting a non-selective ligand to a selective biological tool could be applied to other ligands of interest.
Published: 2013
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