Potent and Orally Active Small-Molecule Inhibitors of the MDM2−p53 Interaction

2009176 citationsJournal Articlegreen Open Access

Authors

Shanghai Yu · University of Michigan–Ann Arbor

Dongguang Qin · University of Michigan–Ann Arbor

Sanjeev Shangary · University of Michigan–Ann Arbor

Jianyong Chen · University of Michigan–Ann Arbor

Guoping Wang · University of Michigan–Ann Arbor

Ke Ding · University of Michigan–Ann Arbor

Donna McEachern

Abstract

We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Compound 5 binds to MDM2 with a K(i) of 0.6 nM, activates p53 at concentrations as low as 40 nM, and potently and selectively inhibits cell growth in tumor cells with wild-type p53 over tumor cells with mutated/deleted p53. Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model.

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Publication Details

Published in: Journal of Medicinal Chemistry

Volume 52, Issue 24, pp. 7970-7973

DOI: 10.1021/jm901400z

Field-Weighted Citation Impact: 4.32

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Potent and Orally Active Small-Molecule Inhibitors of the MDM2−p53 Interaction

Authors

Abstract

Topics & Keywords

Publication Details