| Literature DB >> 19155174 |
Antonella Converso1, Timothy Hartingh, Robert M Garbaccio, Edward Tasber, Keith Rickert, Mark E Fraley, Youwei Yan, Constantine Kreatsoulas, Steve Stirdivant, Bob Drakas, Eileen S Walsh, Kelly Hamilton, Carolyn A Buser, Xianzhi Mao, Marc T Abrams, Stephen C Beck, Weikang Tao, Rob Lobell, Laura Sepp-Lorenzino, Joan Zugay-Murphy, Vinod Sardana, Sanjeev K Munshi, Sylvie Marie Jezequel-Sur, Paul D Zuck, George D Hartman.
Abstract
A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.Entities:
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Year: 2008 PMID： 19155174 DOI： 10.1016/j.bmcl.2008.12.076
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823