PK11000

PK11000 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. PK11000 acts 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. PK11007 induces mainly caspase-independent cell death.

Synonyms:

2-methylsulfonyl-5-chloro-4-pyrimidine carboxylic acid;

2-methanesulfonyl-5-chloro-4-pyrimidinecarboxylic acid;

2-methylsulfonyl-5-chloropyrimidine-4-carboxylic acid;

5-chloro-2-methanesulfonyl-pyrimidine-4-carboxylic acid;

4-carboxy-5-chloro-2-methylsulfonylpyrimidine;

p53 Inhibitors Related Products:

Nutlin-3a; Serdemetan; RITA (NSC 652287); Tenovin-1; Tenovin-6; Tenovin-3; SAR405838 (MI-77301)

[1]. Bauer MR, et al. 2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5271-80.

[2]. Synnott NC, et al. Mutant p53 as a therapeutic target for the treatment of triple-negative breast cancer: Preclinical investigation with the anti-p53 drug, PK11007. Cancer Lett. 2018 Feb 1;414:99-106