chk1 in 3

CHK1-IN-3 是一种检测点激酶 (CHK1) 抑制剂，IC50 值为 0.4 nM。

PROTACFLT3/CHK1 Degrader-1 是一种具有双重目标的PROTAC降解剂，其对FLT3和CHK1的DC50值分别为5.88 nM和4.17 nM。此化合物能够抑制FLT3下游信号因子STAT5(Tyr694)、AKT(Ser473)和ERK(Tyr204)的磷酸化，并降低c-Myc蛋白水平，同时保持p53蛋白的表达。在MV-4-11细胞中，PROTACFLT3/CHK1 Degrader-1 可引发凋亡 (apoptosis)，并在携带MV-4-11皮下异种移植的小鼠中展现出显著的抗肿瘤效能。这种化合物适用于急性髓系白血病 (AML) 的相关研究。

FLT3/CHK1 ligand-1是一种PROTAC靶蛋白配体，可用于合成诸如PROTACFLT3/CHK1 Degrader-1的PROTACs。PROTACFLT3/CHK1 Degrader-1是一种高效的FLT3/CHK1 PROTAC降解剂，展现出抗肿瘤活性。

CHK1-IN-8 (example 3-2) 是一种Chk1抑制剂，对人Chk1的抑制作用具有IC50<10 nM的效果。CHK1-IN-8 适用于癌症研究。

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.