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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