PK11007

PK11007 is a mild thiol alkylator with anticancer activity in several cell lines, especially those with mutationally compromised p53. It effectively kills cancer cells, especially with null or mutant p53 background, and shows only low cytotoxicity toward normal cells. PK11007 acts by two routes: p53 dependent and p53 independent. PK11007 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11007 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. PK11007 induces mainly caspase-independent cell death.