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Current Medicinal Chemistry

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Review Article

Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer

Author(s): Neha Bhatia, Rakesh Khator, Swanand Kulkarni, Yogesh Singh, Pradeep Kumar and Suresh Thareja*

Volume 30, Issue 32, 2023

Published on: 27 December, 2022

Page: [3668 - 3701] Pages: 34

DOI: 10.2174/0929867330666221114103924

Price: $65

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Abstract

Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not only the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MDM2- p53 interaction inhibitors.

Keywords: Murine double minute 2 (MDM2), p53, cancer, MDM2-p53 inhibitor, nutlin, biological efficacy.

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