Mutant Cellular tumor antigen p53 (Mutant p53)

Mutant Cellular tumor antigen p53 (Mutant p53) is the altered form of the p53 protein, a master regulator transcription factor widely known as the "guardian of the genome." In its wild-type state, p53 serves as a critical tumor suppressor by orchestrating cell cycle arrest, DNA repair, and apoptosis in response to cellular stress. However, mutations in the TP53 gene occur in over 50% of human malignancies, leading to the loss of these protective functions and the acquisition of "gain-of-function" (GOF) oncogenic activities. These GOF properties actively promote tumor growth, metastatic potential, chemoresistance, and metabolic reprogramming, such as the Warburg effect. Therapeutically, mutant p53 is an extremely high-value target in oncology, though it was historically considered "undruggable" due to its lack of deep enzymatic binding pockets. Contemporary drug development focuses on small molecules that can stabilize or refold the mutant protein back into its active wild-type conformation or facilitate its degradation to eliminate its oncogenic influence. Leading candidates like eprenetapopt (APR-246) and rezatapopt (PC14586) are currently being evaluated in clinical trials for their ability to restore p53 function and improve survival outcomes in patients with diverse p53-mutated cancers.

Other names

Mutant tumor protein p53mutp53Antigen NY-CO-13 (mutant)Phosphoprotein p53 (mutant)Transformation-related protein 53 (mutant)TP53 (mutant)

Drugs targeting mutant p53 primarily act through three major strategies: pharmacological reactivation of the wild-type conformation in missense mutants (e.g., via covalent binding to cysteine residues), induction of the degradation of stabilized mutant p53 proteins (e.g., via HSP90 or MDM2-mediated pathways), or by promoting translational read-through of nonsense mutations to restore full-length protein production [1, 3, 4, 6, 13].