1. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
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Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2016
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