MDM2-p53 Interaction Inhibitors: The Current State-of-Art and Updated Patent Review (2010-Present)

Recent Pat Anticancer Drug Discov. 2019;14(4):324-369. doi: 10.2174/1574892814666191022163540.

Abstract

Background: Mouse Double Minute 2 protein (MDM2) is a cellular regulator of p53 tumor suppressor (p53). Inhibition of the interaction between MDM2 and p53 proteins is a promising anticancer therapy.

Objective: This updated patent review is an attempt to compile the research and achievements of the various researchers working on small molecule MDM2 inhibitors from 2010 to date. We provide an outlook into the future for therapy based on MDM2 inhibition by presenting an overview of the most relevant patents which have recently appeared in the literature.

Methods: Literature and recent patents focusing on the anticancer potential of MDM2-p53 interaction inhibitors and its applications have been analyzed. We put the main emphasis on the most perspective compounds which are or were examined in clinical trials.

Results: Literature data indicated that MDM2 inhibitors are therapeutically effective in specific types of cancer or non-cancer diseases. A great number of patents and research work around new MDM2- p53 interaction inhibitors, possible combinations, new indications, clinical regimens in previous years prove that this targeted therapy is in the scope of interest for many business and academic research groups.

Conclusion: Novel MDM2 inhibitors thanks to higher potency and better ADME properties have shown effectiveness in preclinical and clinical development however the final improvement of therapeutic potential for MDM2 inhibitors might depend on the useful combination therapy and exploring new cancer and non-cancer indications.

Keywords: Anticancer; LAG3; MDM2 inhibitor; PD-1; combination therapy; molecular targeted therapy; p53; patent..

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Patents as Topic
  • Protein Interaction Domains and Motifs
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2