生物活性

• 描述GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3 and subunit, which plays a key role in many different biological processes including tumorigenesis, cell survival, and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/-catenin signaling^[2][3]. CHIR-98014 (CT98014) is highly selective aminopyrimidine-derivatived inhibitor of GSK-3 with IC50 of 650nM and 580nM for GSK-3 and GSK-3(measured by kinase assays), respectively, and exhibits >1000-fold selectivity for GSK-3 over closely related kinases, such as cdc2. Exposure of insulin receptor–expressing CHO-IR cells or primary rat hepatocytes to CHIR-98014 can result in a 2-3 fold stimulation of the glycogen synthase activity ratio above basal and the EC50 is 106nM and 107nM for CHO-IR cells and rat hepatocytes, respectively. Diabetic and insulin-resistant db/db mice with subcutaneous administration of 30 mg/kg CHIR-98014 exhibited a significant reduction in fasting hyperglycemia within 4 h, as well as improved glucose tolerance accompanied by reduction of plasma insulin levels^[1]. Pre-treatment of 0.6 uM CHIR-98014 for 2 days can induce CD34+CD31+ endothelial progenitor differentiation of 19-9-11 iPSCs cultured on Matrigel in LaSR basal medium before culture in StemPro-34 medium for 3 days^[4].
• 作用机制CHIR-98014 is competitive inhibitor of ATP binding. ^[1]