PK11000

Description: PK11000 is a novel and potent p53-targeting compound and an alkylating agent with anti-tumor activities through activation of unstable p53 (tumor suppressor p53). PK11000 acted by two routes: p53 dependent and p53 independent. PK11000 stabilized p53 in vitro via selective alkylation of two surface-exposed cysteines without compromising its DNA binding activity. Unstable p53 was reactivated by PK11000 in some cancer cell lines, leading to up-regulation of p53 target genes such as p21 and PUMA. More generally, there was cell death that was independent of p53 but dependent on glutathione depletion and associated with highly elevated levels of reactive oxygen species and induction of endoplasmic reticulum (ER) stress, as also found for the anticancer agent PRIMA-1(MET)(APR-246). PK11000 may be a lead for anticancer drugs that target cells with nonfunctional p53 or impaired reactive oxygen species (ROS) detoxification in a wide variety of mutant p53 cells.

References: Proc Natl Acad Sci U S A. 2016 Sep 6; 113(36):E5271-80; Cancer Lett. 2018 Feb 1; 414:99-106.

Related CAS#: 874146-69-7 (PK11007); 38275-34-2 (PK11000)