| Literature DB >> 15715460 |
Bruce L Grasberger1, Tianbao Lu, Carsten Schubert, Daniel J Parks, Theodore E Carver, Holly K Koblish, Maxwell D Cummings, Louis V LaFrance, Karen L Milkiewicz, Raul R Calvo, Diane Maguire, Jennifer Lattanze, Carol F Franks, Shuyuan Zhao, Kannan Ramachandren, Gwendolyn R Bylebyl, Marie Zhang, Carl L Manthey, Eugene C Petrella, Michael W Pantoliano, Ingrid C Deckman, John C Spurlino, Anna C Maroney, Bruce E Tomczuk, Christopher J Molloy, Roger F Bone.
Abstract
HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.Entities:
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Year: 2005 PMID： 15715460 DOI： 10.1021/jm049137g
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446