| Literature DB >> 23628333 |
Peter S Dragovich1, Benjamin P Fauber, Laura B Corson, Charles Z Ding, Charles Eigenbrot, HongXiu Ge, Anthony M Giannetti, Thomas Hunsaker, Sharada Labadie, Yichin Liu, Shiva Malek, Borlan Pan, David Peterson, Keith Pitts, Hans E Purkey, Steve Sideris, Mark Ultsch, Erica VanderPorten, BinQing Wei, Qing Xu, Ivana Yen, Qin Yue, Huihui Zhang, Xuying Zhang.
Abstract
A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50=8.1 μM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.48 μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships.Entities:
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Year: 2013 PMID： 23628333 DOI： 10.1016/j.bmcl.2013.04.001
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823