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Your search keyword '"Bradley P. Morgan"' showing total 3 results
Start Over Author "Bradley P. Morgan" Journal acs medicinal chemistry letters
3 results on '"Bradley P. Morgan"'

1. Discovery of Tirasemtiv, the First Direct Fast Skeletal Muscle Troponin Activator

Author

A Kennedy, Aaron C. Hinken, William F. Browne, Kwan Leung, Matthew Tomlinson, Bradley P Morgan, James J. Hartman, Pu-Ping Lu, Gustave Bergnes, Fady I. Malik, David J. Morgans, Alexander Muci, David Marquez, Marc Garard, Ion Suehiro, Scott Collibee, Kenneth Lee, Donghong Xu, Alan J. Russell, Julia Schaletzky, Raja Kawas, and Darren Hwee

Subjects
0301 basic medicine, Letter, Tirasemtiv, tirasemtiv, Pharmacology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Troponin complex, Drug Discovery, medicine, Amyotrophic lateral sclerosis (ALS), Amyotrophic lateral sclerosis, biology, Activator (genetics), Chemistry, troponin, Organic Chemistry, Skeletal muscle, Metabolic stability, medicine.disease, Troponin, skeletal muscle activator, 030104 developmental biology, medicine.anatomical_structure, imidazo[4,5-b]pyrazin-2-one, biology.protein, 030217 neurology & neurosurgery
Abstract

The identification and optimization of the first activators of fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of 1 for potency, metabolic stability, and physical properties led to the discovery of tirasemtiv (25), which has been extensively characterized in clinical trials for the treatment of amyotrophic lateral sclerosis.

Published
2018

2. Discovery of Omecamtiv Mecarbil the First, Selective, Small Molecule Activator of Cardiac Myosin

Author

Todd Tochimoto, Zhengping Wang, Erica Kraynack, Xiangping Qian, Sheila Sylvester, Ion Suehiro, Alexander Muci, Hong Jiang, S. Corey Valdez, Adam Lewis Tomasi, Smith Whitney W, Kenneth Lee, Robert F. Anderson, Marc Garard, James J. Hartman, Donghong Xu, Hector M. Rodriguez, Guillermo Godinez, Sandra H. Sueoka, Pu-Ping Lu, Scott Collibee, Fady I. Malik, Wenyue Wang, Raja Kawas, Bradley P. Morgan, Nebojsa Djordjevic, Kathleen A. Elias, and David J. Morgans

Subjects
Activator (genetics), business.industry, Organic Chemistry, Cardiac myosin, Pharmacology, medicine.disease, Bioinformatics, Biochemistry, Small molecule, Omecamtiv mecarbil, Heart failure, Drug Discovery, Myosin, medicine, business
Abstract

We report the design, synthesis, and optimization of the first, selective activators of cardiac myosin. Starting with a poorly soluble, nitro-aromatic hit compound (1), potent, selective, and soluble myosin activators were designed culminating in the discovery of omecamtiv mecarbil (24). Compound 24 is currently in clinical trials for the treatment of systolic heart failure.

Published
2010
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3. Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295

Author

Duke M. Fitch, Stephen Schauer, Steven D. Knight, Zhengping Wang, Michael N. Zimmerman, Kurt R. Auger, Roman Sakowicz, Dashyant Dhanak, Han-Jie Zhou, Amita M. Chaudhari, Carrie E. Aroyan, Jeffrey T. Finer, Deping Chai, Jeffrey R. Jackson, Lance Ridgers, Luke W. Ashcraft, Seyed Ahmed, Kenneth Wood, Erin D. Hugger, Jennifer Kuo Chen Huang, Melchor V. Marin, John D. Elliott, Andrew Mcdonald, Cynthia A. Parrish, David Sutton, Ramesh Baliga, Mariela Colón, Lisa D. Belmont, Carla A. Donatelli, Nicholas D. Adams, Joelle Lorraine Burgess, Hong Jiang, Rosanna Tedesco, Bing Yao, Jianchao Wang, Kevin J. Duffy, Gustave Bergnes, Xiangping Qian, Chiu-Mei Sung, David J. Morgans, Robert A. Copeland, Bradley P. Morgan, Michael G. Darcy, Jeffrey D. Carson, Latesh Lad, Ken A. Newlander, Lusong Luo, Daniel W. Pierce, and Schmidt Stanley J

Subjects
Antitumor activity, business.industry, Organic Chemistry, Cancer, Pharmacology, medicine.disease, Biochemistry, chemistry.chemical_compound, chemistry, In vivo, Drug Discovery, Centromere, medicine, Benzamide, business, Mitosis
Abstract

Inhibition of mitotic kinesins represents a novel approach for the discovery of a new generation of anti-mitotic cancer chemotherapeutics. We report here the discovery of the first potent and selective inhibitor of centromere-associated protein E (CENP-E) 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide (GSK923295; 1), starting from a high-throughput screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated broad antitumor activity in vivo and is currently in human clinical trials.

Published
2009

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