Document Report Card

ID: ALA1154717

Journal: J Med Chem

Title: Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction.

Authors: Yu S, Qin D, Shangary S, Chen J, Wang G, Ding K, Ding K, McEachern D, Qiu S, Nikolovska-Coleska Z, Miller R, Kang S, Yang D, Wang S.

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.

CiteXplore: 19928922

DOI: 10.1021/jm901400z