Colletofragarone A2, isolated from the fungus Colletotrichum sp. (13S020), exhibits anti-cancer activity by inhibiting mutant p53 and HSP90. It promotes the degradation and aggregation of mutant p53, in turn suppressing tumor growth in vivo [1].

Colletofragarone A2 exhibits selective cytotoxicity towards cells harboring p53 R175H structural mutants, displaying higher efficacy than against other p53 variants, such as DNA-contact mutants, wild-type, or null p53 cells (0.05-5 µM; 72 h). It effectively reduces mutant p53 levels by facilitating its degradation in SK-BR-3 cells with the p53 R175H mutation (2 µM; 8 h). Furthermore, when combined with MG-132 (10 µM), Colletofragarone A2 induces the accumulation of aggregated mutant p53 at concentrations of either 2 or 4 µM over 4 hours.

Colletofragarone A2, administered intratumorally at 0.35 mM and 100 μL daily for 13 days, significantly reduces tumor growth in mice inoculated with HuCCT1 cells harboring the p53 R175H mutation [1].