chk1-in-3

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

CHK1-IN-8 (example 3-2) is an inhibitor of Chk1, exhibiting an IC50 of less than 10 nM against human Chk1. It is applicable for cancer research.

PROTAC ATRdegrader-3 is a potent CRBN-based ATR PROTAC degrader with a DC50 of 127 nM. This compound also degrades CHK1, with a corresponding DC50 of 135 nM. PROTAC ATRdegrader-3 inhibits the proliferation, migration, and invasion of cancer cells, induces apoptosis, and causes S phase arrest and DNA damage. It effectively suppresses tumor growth in LoVo xenograft mouse models with negligible toxicity. PROTAC ATRdegrader-3 is applicable in research related to colorectal cancer.

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

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.