Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53 protein-protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase clinical trials for the treatment of human cancers. Here, we review the design, synthesis, properties, preclinical, and clinical studies of these clinical-stage MDM2 inhibitors.
University of Michigan Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
Yujun
Y
Zhao
Angelo
A
Aguilar
Denzil
D
Bernard
Shaomeng
S
Wang
D000818:Animals; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2