| Literature DB >> 24900171 |
Xiangping Qian1, Andrew McDonald1, Han-Jie Zhou1, Nicholas D Adams2, Cynthia A Parrish2, Kevin J Duffy2, Duke M Fitch2, Rosanna Tedesco2, Luke W Ashcraft1, Bing Yao1, Hong Jiang1, Jennifer K Huang1, Melchor V Marin1, Carrie E Aroyan1, Jianchao Wang1, Seyed Ahmed1, Joelle L Burgess2, Amita M Chaudhari2, Carla A Donatelli2, Michael G Darcy2, Lance H Ridgers2, Ken A Newlander2, Stanley J Schmidt2, Deping Chai2, Mariela Colón2, Michael N Zimmerman2, Latesh Lad1, Roman Sakowicz1, Stephen Schauer1, Lisa Belmont1, Ramesh Baliga1, Daniel W Pierce1, Jeffrey T Finer1, Zhengping Wang1, Bradley P Morgan1, David J Morgans1, Kurt R Auger2, Chiu-Mei Sung2, Jeff D Carson2, Lusong Luo2, Erin D Hugger2, Robert A Copeland2, David Sutton2, John D Elliott2, Jeffrey R Jackson2, Kenneth W Wood1, Dashyant Dhanak2, Gustave Bergnes1, Steven D Knight2.
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.Entities:
Keywords: CENP-E; GSK923295; inhibitor; mitotic kinesin
Year: 2010 PMID： 24900171 PMCID： PMC4007900 DOI： 10.1021/ml900018m
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345