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Abstract
Restoration of wild-type p53 expression triggers cell death and eliminates tumors
in vivo. The identification of mutant p53-reactivating small molecules such as PRIMA-1
opens possibilities for the development of more efficient anticancer drugs. Although
the biological effects of PRIMA-1 are well demonstrated, little is known about its
molecular mechanism of action. We show here that PRIMA-1 is converted to compounds
that form adducts with thiols in mutant p53. Covalent modification of mutant p53 per
se is sufficient to induce apoptosis in tumor cells. These findings might facilitate
the design of more potent and specific mutant p53-targeting anticancer drugs.