CHK1-IN-3 is an inhibitor of checkpoint kinase 1 (CHK1; IC50: 0.4 nM).

PD-321852 is a small-molecule Chk1 inhibitor, which potentiates gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD-321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines.

Potent Chk2 inhibitor (IC50 = 3 nM). Shows >63-fold selectivity for Chk1 over Chk2 and a panel of 84 other kinases. Inhibits Chk2 activation in response to etoposide-induced DNA damage in HT29 cells. Blocks ionizing radiation-induced apoptosis of mouse thymocytes. Caldwell et al (2011) Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J.Med.Chem. 54 580 PMID:21186793