Search

Your search keyword '"Bugianesi, Randal M."' showing total 22 results
Start Over Author "Bugianesi, Randal M."
22 results on '"Bugianesi, Randal M."'

1. Analgesic Effects of a Substituted N-Triazole Oxindole (TROX-1), a State-Dependent, Voltage-Gated Calcium Channel 2 Blocker

Author

Abbadie, Catherine, McManus, Owen B., Sun, Shu-Yu, Bugianesi, Randal M., Dai, Ge, Haedo, Rodolfo J., Herrington, James B., Kaczorowski, Gregory J., Smith, McHardy M., Swensen, Andrew M., Warren, Vivien A., Williams, Brande, Arneric, Stephen P., Eduljee, Cyrus, Snutch, Terrance P., Tringham, Elizabeth W., Jochnowitz, Nina, Liang, Annie, Euan MacIntyre, D., McGowan, Erin, Mistry, Shruti, White, Valerie V., Hoyt, Scott B., London, Clare, Lyons, Kathryn A., Bunting, Patricia B., Volksdorf, Sylvia, and Duffy, Joseph L.

Published
2010
Full Text
View/download PDF

2. Identification of a new class of inhibitors of the voltage-gated potassium channel, K(sub)v1.3, with immunosuppressant properties

Author

Schmalhofer, William A., Bao, Jianming, McManus, Owen B., Card, Orson Scott, Matyskiela, Mary, Wunderler, Denise, Bugianesi, Randal M., Felix, John P., Hanner, Markus, Linde-Arias, Ana-Rosa, Ponte, Cristiano G., Velasco, Lucia, Koo, Gloria, Staruch, Mary Jo, Miao, Shouwu, Parsons, William H., Rupprecht, Kathleen, Slaughter, Robert S., Kaczorowski, Gregory J., and Garcia, Maria L.

Subjects
Potassium channels -- Physiological aspects, Enzyme inhibitors -- Physiological aspects, Protein binding -- Physiological aspects, T cells -- Physiological aspects, Structure-activity relationships (Biochemistry) -- Analysis, Biological sciences, Chemistry
Abstract

Research describes a disubstituted cyclohexyl analogue that blocks the voltage-gated K(sub)v1.3 potassium channels, inhibits ditritiocorreolide binding to channel proteins, and suppresses the calcium-dependent T cell activation pathway.

Published
2002

3. Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3

Author

Felix, John P., Bugianesi, Randal M., Schmalhofer, William A., Borris, Robert, Goetz, Michael A., Hensens, Otto D., Bao, Jian-Ming, Kayser, Frank, Parsons, William H., Rupprecht, Kathleen, Garcia, Maria L., Kaczorowski, Gregory J., and Slaughter, Robert S.

Subjects
Potassium channels -- Research, Ion channels -- Research, Immunosuppressive agents -- Research, Chemical inhibitors -- Research, T cells -- Research, Biological sciences, Chemistry
Abstract

A study on the immunosuppression of voltage-gated delayed rectifier potassium channel called Kv1.3, found in human T lymphocytes, presents the initial biochemical characterization of correolide and several other structurally related molecules as inhibitors of Kv1.3. The experiment also reports on a radiolabeled correolide derivative, [3H]C20-29 dihydrocorreolide, which is useful as a ligand for the study of KV1 family channels. Results are discussed.

Published
1999

4. Blockers of the Delayed-Rectifier Potassium Current in Pancreatic β-Cells Enhance Glucose-Dependent Insulin Secretion

Author

Herrington, James, Zhou, Yun-Ping, Bugianesi, Randal M., Dulski, Paula M., Feng, Yue, Warren, Vivien A., Smith, McHardy M., Kohler, Martin G., Garsky, Victor M., Sanchez, Manuel, Wagner, Michael, Raphaelli, Kristin, Banerjee, Priya, Ahaghotu, Chinweze, Wunderler, Denise, Priest, Birgit T., Mehl, John T., Garcia, Maria L., McManus, Owen B., Kaczorowski, Gregory J., and Slaughter, Robert S.

Published
2006

5. Margatoxin binds to a homomultimer of Kv1.3 channels in jurkat cells. Comparison with Kv1.3 expressed in CHO cells

Author

Helms, Lisa M.H., Felix, John P., Bugianesi, Randal M., Garcia, Maria L., Stevens, Scott, Leonard, Reid J., Knaus, Hans-Gunther, Koch, Robert, Wanner, Siegmund G., Kaczorowski, Gregory J., and Slaughter, Robert S.

Subjects
Lymphocytes -- Research, Biological sciences, Chemistry
Abstract

The binding of monoiodotyrosinyl margatoxin to plasma membranes prepared from either Jurka cells, a human leukemic T cell line, or CHO cells stably transfected with the Shaker-type voltage-gated K+ channel, has been determined. The results showed that the lymphocyte(125I)MgTX receptor is homomultimer of Kv1.3 subunits.

Published
1997

8. Substitution of a single residue in Stichodactyla helianthus peptide, Shk-Dap(sup)22, reveals a novel pharmacological profile

Author

Middleton, Richard E., Sanchez, Manuel, Linde, Ana-Rosa, Bugianesi, Randal M., Dai, Ge, Felix, John P., Koprak, Sam L., Staruch, Mary Jo, Bruguera, Marc, Cox, Rachael, Ghosh, Amrita, Hwang, Jeremy, Jones, Simmonette, Kohler, Martin, Slaughter, Robert S., Mcmanus, Owen B., Kaczorowski, Gregory J., and Garcia, Maria L.

Subjects
Immunosuppression -- Analysis, Potassium channels -- Chemical properties, Potassium channels -- Structure, Substitution reactions -- Analysis, Venom -- Research, Biological sciences, Chemistry
Abstract

Research reveals that substitution of lysine22 with a diaminopropionic acid residue in Stichodactyla helianthus venom ShK peptide, ShK-Dap22, changes the in vivo immunosuppressant efficacy of other potassium channel blockers. Furthermore, from a pharmacological point of view ShK-Dap22 may cause side effects due to its interaction with other blockers.

Published
2003

9. Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure–Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program

Author

Zhang, Ting, primary, Liu, Yong, additional, Yang, Xianshu, additional, Martin, Gary E., additional, Yao, Huifang, additional, Shang, Jackie, additional, Bugianesi, Randal M., additional, Ellsworth, Kenneth P., additional, Sonatore, Lisa M., additional, Nizner, Peter, additional, Sherer, Edward C., additional, Hill, Susan E., additional, Knemeyer, Ian W., additional, Geissler, Wayne M., additional, Dandliker, Peter J., additional, Helmy, Roy, additional, and Wood, Harold B., additional

Published
2016
Full Text
View/download PDF

10. Improved Cav2.2 Channel Inhibitors through a gem-Dimethylsulfone Bioisostere Replacement of a Labile Sulfonamide

Author

Shao, Pengcheng P., primary, Ye, Feng, additional, Chakravarty, Prasun K., additional, Herrington, James B., additional, Dai, Ge, additional, Bugianesi, Randal M., additional, Haedo, Rodolfo J., additional, Swensen, Andrew M., additional, Warren, Vivien A., additional, Smith, McHardy M., additional, Garcia, Maria L., additional, McManus, Owen B., additional, Lyons, Kathryn A., additional, Li, Xiaohua, additional, Green, Mitchell, additional, Jochnowitz, Nina, additional, McGowan, Erin, additional, Mistry, Shruti, additional, Sun, Shu-Yu, additional, Abbadie, Catherine, additional, Kaczorowski, Gregory J., additional, and Duffy, Joseph L., additional

Published
2013
Full Text
View/download PDF

11. Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program.

Author

Ting Zhang, Yong Liu, Xianshu Yang, Martin, Gary E., Huifang Yao, Jackie Shang, Bugianesi, Randal M., Ellsworth, Kenneth P., Sonatore, Lisa M., Nizner, Peter, Sherer, Edward C., Hill, Susan E., Knemeyer, Ian W., Geissler, Wayne M., Dandliker, Peter J., Helmy, Roy, and Wood, Harold B.

Published
2016
Full Text
View/download PDF

12. Aminopiperidine Sulfonamide Cav2.2 Channel Inhibitors for the Treatment of Chronic Pain

Author

Shao, Pengcheng P., primary, Ye, Feng, additional, Chakravarty, Prasun K., additional, Varughese, Deepu J., additional, Herrington, James B., additional, Dai, Ge, additional, Bugianesi, Randal M., additional, Haedo, Rodolfo J., additional, Swensen, Andrew M., additional, Warren, Vivien A., additional, Smith, McHardy M., additional, Garcia, Maria L., additional, McManus, Owen B., additional, Lyons, Kathryn A., additional, Li, Xiaohua, additional, Green, Mitchell, additional, Jochnowitz, Nina, additional, McGowan, Erin, additional, Mistry, Shruti, additional, Sun, Shu-Yu, additional, Abbadie, Catherine, additional, Kaczorowski, Gregory J., additional, and Duffy, Joseph L., additional

Published
2012
Full Text
View/download PDF

13. Characterization of the SubstitutedN-Triazole Oxindole TROX-1, a Small-Molecule, State-Dependent Inhibitor of Cav2 Calcium Channels

Author

Swensen, Andrew M., primary, Herrington, James, additional, Bugianesi, Randal M., additional, Dai, Ge, additional, Haedo, Rodolfo J., additional, Ratliff, Kevin S., additional, Smith, McHardy M., additional, Warren, Vivien A., additional, Arneric, Stephen P., additional, Eduljee, Cyrus, additional, Parker, David, additional, Snutch, Terrance P., additional, Hoyt, Scott B., additional, London, Clare, additional, Duffy, Joseph L., additional, Kaczorowski, Gregory J., additional, and McManus, Owen B., additional

Published
2011
Full Text
View/download PDF

15. A Cell-Sparing Electric Field Stimulation Technique for High-Throughput Screening of Voltage-Gated Ion Channels

Author

Bugianesi, Randal M., primary, Augustine, Paul R., additional, Azer, Karim, additional, Dufresne, Claude, additional, Herrington, James, additional, Kath, Gary S., additional, McManus, Owen B., additional, Napolitano, Christopher S., additional, Rush, Alison, additional, Sachs, Jeff, additional, Simpson, Neal, additional, Wismer, Michael K., additional, Kaczorowski, Gregory J., additional, and Slaughter, Robert S., additional

Published
2006
Full Text
View/download PDF

16. A High-Capacity Membrane Potential FRET-Based Assay for NaV1.8 Channels

Author

Liu, Chou J., primary, Priest, Birgit T., additional, Bugianesi, Randal M., additional, Dulski, Paula M., additional, Felix, John P., additional, Dick, Ivy E., additional, Brochu, Richard M., additional, Knaus, Hans-Guenther, additional, Middleton, Richard E., additional, Kaczorowski, Gregory J., additional, Slaughter, Robert S., additional, Garcia, Maria L., additional, and Köhler, Martin G., additional

Published
2006
Full Text
View/download PDF

17. Stichodactyla helianthusPeptide, a Pharmacological Tool for Studying Kv3.2 Channels

Author

Yan, Lizhen, primary, Herrington, James, additional, Goldberg, Ethan, additional, Dulski, Paula M., additional, Bugianesi, Randal M., additional, Slaughter, Robert S., additional, Banerjee, Priya, additional, Brochu, Richard M., additional, Priest, Birgit T., additional, Kaczorowski, Gregory J., additional, Rudy, Bernardo, additional, and Garcia, Maria L., additional

Published
2005
Full Text
View/download PDF

18. Potent Kv1.3 inhibitors from correolide—modification of the C18 position

Author

Bao, Jianming, primary, Miao, Shouwu, additional, Kayser, Frank, additional, Kotliar, Andrew J., additional, Baker, Robert K., additional, Doss, George A., additional, Felix, John P., additional, Bugianesi, Randal M., additional, Slaughter, Robert S., additional, Kaczorowski, Gregory J., additional, Garcia, Maria L., additional, Ha, Sookhee N., additional, Castonguay, Laurie, additional, Koo, Gloria C., additional, Shah, Kashmira, additional, Springer, Marty S., additional, Staruch, Mary Jo, additional, Parsons, William H., additional, and Rupprecht, Kathleen M., additional

Published
2005
Full Text
View/download PDF

20. Identification of a New Class of Inhibitors of the Voltage-Gated Potassium Channel, K[sub v]1.3, with Immunosuppressant Properties.

Author

Schmalhofer, William A., Jianming Bao, McManus, Owen B., Green, Brian, Matyskiela, Mary, Wunderler, Denise, Bugianesi, Randal M., Felix, John P., Hanner, Markus, Linde-Arias, Ana-Rosa, Ponte, Cristiano G., Velasco, Lucia, Koo, Gloria, Staruch, Mary Jo, Shouwu Miao, Parsons, William H., Rupprecht, Kathleen, and Slaughter, Robert S.

Published
2002
Full Text
View/download PDF

21. Characterization of the Substituted N-Triazole Oxindole TROX-1, a Small-Molecule, State-Dependent Inhibitor of Cav2 Calcium Channels

Author

Swensen, Andrew M., Herrington, James, Bugianesi, Randal M., Dai, Ge, Haedo, Rodolfo J., Ratliff, Kevin S., Smith, McHardy M., Warren, Vivien A., Arneric, Stephen P., Eduljee, Cyrus, Parker, David, Snutch, Terrance P., Hoyt, Scott B., London, Clare, Duffy, Joseph L., Kaczorowski, Gregory J., and McManus, Owen B.

Abstract

Biological, genetic, and clinical evidence provide validation for N-type calcium channels (CaV2.2) as therapeutic targets for chronic pain. A state-dependent CaV2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl CaV2.2 inhibitor used clinically. Supporting this notion, we recently reported that in preclinical models, the state-dependent CaV2 inhibitor (3R)-5-(3-chloro-4-fluorophenyl)-3-methyl-3-(pyrimidin-5-ylmethyl)-1-(1H-1,2,4-triazol-3-yl)-1,3-dihydro-2H-indol-2-one (TROX-1) has an improved therapeutic window compared with ziconotide. Here we characterize TROX-1 inhibition of Cav2.2 channels in more detail. When channels are biased toward open/inactivated states by depolarizing the membrane potential under voltage-clamp electrophysiology, TROX-1 inhibits CaV2.2 channels with an IC50of 0.11 μM. The voltage dependence of CaV2.2 inhibition was examined using automated electrophysiology. TROX-1 IC50values were 4.2, 0.90, and 0.36 μM at −110, −90, and −70 mV, respectively. TROX-1 displayed use-dependent inhibition of CaV2.2 with a 10-fold IC50separation between first (27 μM) and last (2.7 μM) pulses in a train. In a fluorescence-based calcium influx assay, TROX-1 inhibited CaV2.2 channels with an IC50of 9.5 μM under hyperpolarized conditions and 0.69 μM under depolarized conditions. Finally, TROX-1 potency was examined across the CaV2 subfamily. Depolarized IC50values were 0.29, 0.19, and 0.28 μM by manual electrophysiology using matched conditions and 1.8, 0.69, and 1.1 μM by calcium influx for CaV2.1, CaV2.2, and CaV2.3, respectively. Together, these in vitro data support the idea that a state-dependent, non–subtype-selective CaV2 channel inhibitor can achieve an improved therapeutic window over the relatively state-independent CaV2.2-selective inhibitor ziconotide in preclinical models of chronic pain.

Published
2012
Full Text
View/download PDF

22. Stichodactyla helianthus Peptide, a Pharmacological Tool for Studying Kv3.2 Channels

Author

Yan, Lizhen, Herrington, James, Goldberg, Ethan, Dulski, Paula M., Bugianesi, Randal M., Slaughter, Robert S., Banerjee, Priya, Brochu, Richard M., Priest, Birgit T., Kaczorowski, Gregory J., Rudy, Bernardo, and Garcia, Maria L.

Abstract

Voltage-gated potassium (Kv) channels regulate many physiological functions and represent important therapeutic targets in the treatment of several clinical disorders. Although some of these channels have been well-characterized, the study of others, such as Kv3 channels, has been hindered because of limited pharmacological tools. The current study was initiated to identify potent blockers of the Kv3.2 channel. Chinese hamster ovary (CHO)-K1 cells stably expressing human Kv3.2b (CHO-K1.hKv3.2b) were established and characterized. Stichodactyla helianthus peptide (ShK), isolated from S. helianthus venom and a known high-affinity blocker of Kv1.1 and Kv1.3 channels, was found to potently inhibit 86Rb+ efflux from CHO-K1.hKv3.2b (IC50 ∼ 0.6 nM). In electrophysiological recordings of Kv3.2b channels expressed in Xenopus laevis oocytes or in planar patch-clamp studies, ShK inhibited hKv3.2b channels with IC50 values of ∼0.3 and 6 nM, respectively. Despite the presence of Kv3.2 protein in human pancreatic β cells, ShK has no effect on the Kv current of these cells, suggesting that it is unlikely that homotetrameric Kv3.2 channels contribute significantly to the delayed rectifier current of insulin-secreting cells. In mouse cortical GABAergic fast-spiking interneurons, however, application of ShK produced effects consistent with the blockade of Kv3 channels (i.e., an increase in action potential half-width, a decrease in the amplitude of the action potential after hyperpolarization, and a decrease in maximal firing frequency in response to depolarizing current injections). Taken together, these results indicate that ShK is a potent inhibitor of Kv3.2 channels and may serve as a useful pharmacological probe for studying these channels in native preparations.

Published
2005

Catalog

Books, media, physical & digital resources
See catalog results