Description
CHIR-98014 can inhibit GSK-3alpha and GSK-3beta with Ki of 0.65 nM and 0.58 nM.
Storage
2 years at -20 centigrade
Targets
GSK-3alpha, GSK-3beta
Molecular Formula
C20H17Cl2N9O2
Chemical Name
N2-(2-(4-(2,4-dichlorophenyl)-5-(1H-imidazol-1-yl)pyrimidin-2-ylamino)ethyl)-5-nitropyridine-2,6-diamine
Solubility
DSMO 4 mg/mL Water
In vitro
CHIR-98014 can inhibit GSK-3alpha and GSK-3beta with Ki of 0.65 nM and 0.58 nM. CHIR-98014 is a ATP binding competitive inhibitor and shows 500-fold to 10,000-fold selectivity for GSK-3 versus 20 other protein kinases. CHIR 98014 also showed similar potency against the highly homologous and isoforms of GSK-3, it is noteworthy that they strongly discriminated between GSK-3 and its closest homologs cdc2 and erk2. CHIR-98014 can activate glycogen synthase at approximately 100 nmol/l in cultured CHO cells transfected with the insulin receptor.
In vivo
In primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. CHIR-98014 can enhance insulin-stimulated glucose transport in type 1 skeletal muscle from the insulin-resistant ZDF rats but not from insulin-sensitive lean Zucker rats. Single oral doses of CHIR-98014 (30-48 mg/kg) rapidly lowered blood glucose levels and improved glucose disposal after oral or intravenous glucose challenges in ZDF rats and db/db mice, without causing hypoglycemia or markedly elevating insulin.
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