Document Report Card

ID: ALA2176930

Journal: J Med Chem

Title: Structure-based design of novel inhibitors of the MDM2-p53 interaction.

Authors: Rew Y, Sun D, Gonzalez-Lopez De Turiso F, Bartberger MD, Beck HP, Canon J, Chen A, Chow D, Deignan J, Fox BM, Gustin D, Huang X, Jiang M, Jiao X, Jin L, Kayser F, Kopecky DJ, Li Y, Lo MC, Long AM, Michelsen K, Oliner JD, Osgood T, Ragains M, Saiki AY, Schneider S, Toteva M, Yakowec P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Medina JC, Olson SH.

Abstract: Structure-based rational design led to the discovery of novel inhibitors of the MDM2-p53 protein-protein interaction. The affinity of these compounds for MDM2 was improved through conformational control of both the piperidinone ring and the appended N-alkyl substituent. Optimization afforded 29 (AM-8553), a potent and selective MDM2 inhibitor with excellent pharmacokinetic properties and in vivo efficacy.

CiteXplore: 22524527

DOI: 10.1021/jm300354j