p53: An Attractive Therapeutic Target for Cancer

Author(s): Krupa R. Patel, Hitesh D. Patel*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 22 , 2020


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Abstract:

Cancer is a leading cause of death worldwide. It initiates when cell cycle regulatory genes lose their function either by environmental and/or by internal factors. Tumor suppressor protein p53, known as “Guardian of genome”, plays a central role in maintaining genomic stability of the cell. Mutation of TP53 is documented in more than 50% of human cancers, usually by overexpression of negative regulator protein MDM2. Hence, reactivation of p53 by blocking the protein-protein interaction between the murine double minute 2 (MDM2) and the tumor suppressor protein p53 has become the most promising therapeutic strategy in oncology. Several classes of small molecules have been identified as potent, selective and efficient p53-MDM2 inhibitors. Herein, we review the druggability of p53-MDM2 inhibitors and their optimization approaches as well as clinical candidates categorized by scaffold type.

Keywords: Cancer, p53 Tumor suppressor protein, Mutation, p53-MDM2 protein-protein interaction, Small molecule inhibitors, p53 reactivation.

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VOLUME: 27
ISSUE: 22
Year: 2020
Published on: 20 June, 2019
Page: [3706 - 3734]
Pages: 29
DOI: 10.2174/1573406415666190621094704
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