Title:p53: An Attractive Therapeutic Target for Cancer
Volume: 27
Issue: 22
Author(s): Krupa R. Patel and Hitesh D. Patel*
Affiliation:
- Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat,India
Keywords:
Cancer, p53 Tumor suppressor protein, Mutation, p53-MDM2 protein-protein interaction, Small molecule
inhibitors, p53 reactivation.
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.
