78P Small molecule compounds targeting the p53 mutants

Abstract

The tumor suppressor p53 is inactivated by mutation in about half of all tumors, making mutant p53 a prime target for cancer therapy. Missense mutations R248W, R273H and R248Q are included in the five most frequent p53 mutations and in total lead to more than 630 000 new diagnosed cases of tumor diseases in the world every year. These mutations, located at or near the protein-DNA interface, lead to p53 inactivation by loss of direct p53-DNA interactions, and by causing conformational changes in the protein, resulting in lowering its stability.