1352063-19-4Relevant articles and documents
Structure-based design of novel inhibitors of the MDM2-p53 interaction
Rew, Yosup,Sun, Daqing,Gonzalez-Lopez De Turiso, Felix,Bartberger, Michael D.,Beck, Hilary P.,Canon, Jude,Chen, Ada,Chow, David,Deignan, Jeffrey,Fox, Brian M.,Gustin, Darin,Huang, Xin,Jiang, Min,Jiao, Xianyun,Jin, Lixia,Kayser, Frank,Kopecky, David J.,Li, Yihong,Lo, Mei-Chu,Long, Alexander M.,Michelsen, Klaus,Oliner, Jonathan D.,Osgood, Tao,Ragains, Mark,Saiki, Anne Y.,Schneider, Steve,Toteva, Maria,Yakowec, Peter,Yan, Xuelei,Ye, Qiuping,Yu, Dongyin,Zhao, Xiaoning,Zhou, Jing,Medina, Julio C.,Olson, Steven H.
, p. 4936 - 4954 (2012/08/07)
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.