P53 mdm2 inhibitors.
The protein-protein interaction (PPI) between p53 and its negative regulator MDM2 comprises one of the most important and intensely studied PPI's involved in preventing the initiation of cancer. The interaction between p53 and MDM2 is conformation-based and is tightly regulated on multiple levels. Due to the Angstrom level structural insight there is a reasonable understanding of the structural requirements needed for a molecule to bind to MDM2 and successfully inhibit the p53/MDM2 interaction. The current review summarizes the binding characteristics of the different disclosed small molecules for inhibition of MDM2 with a co-crystal structure. Synthetic access to these compounds as well as their derivatives are described in detail.
University of Pittsburgh, Department of Pharmaceutical Sciences, Pittsburgh, PA 15261, USA.
Kareem
K
Khoury
Alex
A
Dömling
D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism
D054852:Small Molecule Libraries; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2