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Your search keyword '"Mdm2 p53"' showing total 2 results
Start Over Descriptor "Mdm2 p53" Journal bioorganic & medicinal chemistry letters
2 results on '"Mdm2 p53"'

1. Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors

Author

Alexander G. Tonevitsky, Alexander G. Majouga, Maksim E. Kukushkin, Mark S. Veselov, Yan A. Ivanenkov, Alexey E. Machulkin, Elena K. Beloglazkina, Nina V. Chufarova, Elizaveta S. Chernyaginab, Sergei V. Vasilevski, Anton S. Vanzcool, Nikolay V. Zyk, Olga A. Dontsova, Alexander L. Rusanov, Dmitry A. Skvortsov, and A. A. Khutornenko

Subjects
Models, Molecular, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Antineoplastic Agents, Molecular Dynamics Simulation, Biochemistry, Small Molecule Libraries, Structure-Activity Relationship, Neoplasms, Drug Discovery, Tumor Cells, Cultured, Humans, Mdm2 p53, Molecular Biology, Cell Proliferation, Biological evaluation, Molecular Structure, Chemistry, Organic Chemistry, Diastereomer, Regioselectivity, Proto-Oncogene Proteins c-mdm2, Combinatorial chemistry, Small molecule, Design synthesis, Drug Design, Molecular Medicine, Tumor Suppressor Protein p53
Abstract

Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can therefore be reasonably regarded as promising anticancer therapeutics.

Published
2015
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2. Optimization beyond AMG 232: Discovery and SAR of sulfonamides on a piperidinone scaffold as potent inhibitors of the MDM2-p53 protein–protein interaction

Author

Lawrence R. McGee, Jeffrey T. Mihalic, Yingcai Wang, Mei-Chu Lo, Jing Zhou, Steven H. Olson, Xiaoqi Chen, Frank Kayser, Jiang Zhu, Ada Chen, Jeffrey Deignan, Jonathan D. Oliner, Alexander M. Long, Daqing Sun, Ming Yu, Xin Huang, Qiuping Ye, Jiwen Jim Liu, Peter Yakowec, and Julio C. Medina

Subjects
Models, Molecular, Scaffold, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Acetates, Pharmacology, Crystallography, X-Ray, Biochemistry, Protein–protein interaction, Structure-Activity Relationship, Drug Discovery, medicine, Animals, Humans, Mdm2 p53, Molecular Biology, Piperidones, Sulfonamides, Dose-Response Relationship, Drug, Chemistry, Organic Chemistry, Sulfonamide (medicine), Proto-Oncogene Proteins c-mdm2, Rats, Molecular Medicine, Drug Screening Assays, Antitumor, Tumor Suppressor Protein p53, Protein Binding, medicine.drug
Abstract

We recently reported on the discovery of AMG 232, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. AMG 232 is being evaluated in human clinical trials for cancer. Continued exploration of the N-alkyl substituent of this series, in an effort to optimize interactions with the MDM2 glycine-58 shelf region, led to the discovery of sulfonamides such as compounds 31 and 38 that have similar potency, hepatocyte stability and rat pharmacokinetic properties to AMG 232.

Published
2014
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