Krupa R. Patel and Hitesh D. Patel* Pages 3706 - 3734 ( 29 )
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.
Cancer, p53 Tumor suppressor protein, Mutation, p53-MDM2 protein-protein interaction, Small molecule inhibitors, p53 reactivation.
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat, Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad 380009, Gujarat