PK11007 is a p53 targeting compound, has anti-tumor activities through activation of unstable p53.
PK11007 (15-30 µM) reduces the viability of mutant p53 cell lines MKN1 (V143A), HUH-7 (Y220C), NUGC-3 (Y220C), and SW480 (R273H/P309S). PK11007 also shows inhibitory activities against the p53 wt cancer cell lines HUH-6 and NUGC-4, as well as the fibroblast cell line WI-38 only at high concentrations (60 and 120 µM). PK11007 increases levels of p53 target genes and activates the unfolded protein response pathway. PK11007 also increases p53 activity in HUH-6 and NUGC-4 cells. PK11007 induces cell death via caspase-independent pathways. PK11007 (30, 60 µM) induces reactive oxygen species (ROS) especially in mutant p53 cells[1]. PK11007 inhibits the proliferation of a panel of 17 breast cell lines, with IC50s ranging from 2.3 to 42.2 μM[2].
[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