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.
Small molecule inhibition of MDM2p53 interaction augments radiation response in human tumors.Current Drug Targets. Title:Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed. Volume: 20 Issue: 11.
In this study, we sought to investigate the preclinical activity of the MDM2 antagonist, Nutlin-3a, in Philadelphia positive (Ph +) and negative (Ph ) leukemic cell line models, and primary B-acute lymphoblastic leukemia (ALL) patient samples. Here, we identify a class of small molecules that can potently inhibit p53 interactions with both MDM2 and MDMX by induced protein dimerization and effectively restore p53 activity in MDMX-overexpressing cancer cells. This review presents the last decade of studies on the synthesis of various types of small-molecule inhibitors of the p53 Mouse double minute 2 homolog (MDM2) proteinprotein interaction. t present, disrupting p53-MDM2 interactions through small molecule ligands is a promising approach to safe treatment and management of human cancer. Tumor cells unlike the normal cells, are rapidly evolving affecting the efficacy of many approved anti-cancer agents due to drug resistance. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field.
This review presents the last decade of studies on the synthesis of various types of small-molecule inhibitors of the p53 Mouse double minute 2 homolog (MDM2) proteinprotein interaction.
Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes.
