chk1 in 3

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

PROTACFLT3/CHK1 Degrader-1 is a PROTAC agent targeting FLT3 and CHK1, with DC50 values of 5.88 nM (FLT3) and 4.17 nM (CHK1). It inhibits the phosphorylation of downstream signaling effectors STAT5(Tyr694), AKT(Ser473), and ERK(Tyr204) of FLT3, reduces c-Myc protein levels, and maintains p53 protein expression. Additionally, PROTACFLT3/CHK1 Degrader-1 induces apoptosis in MV-4-11 cells and demonstrates significant antitumor activity in mice with MV-4-11 xenografts. This compound is applicable in acute myeloid leukemia (AML) research.

FLT3/CHK1 ligand-1 is a PROTAC target protein ligand used in the synthesis of PROTACs, such as [PROTAC FLT3/CHK1 Degrader-1]. [PROTAC FLT3/CHK1 Degrader-1] functions as a potent FLT3/CHK1 PROTAC degrader with antitumor activity.

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.