Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials.

ABSTRACT: p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53-MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical develop

SUBMITTER: Zhu H 

PROVIDER: S-EPMC9277894 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature