Highly potent and selective GSK-3 inhibitor (IC50values are 0.58 and 0.65 nM for the β and α isoforms, respectively). Exhibits >500-fold selectivity for GSK-3β over a range of other kinases. Improves insulin sensitivity of muscle strips from diabetic rats
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
Inhibitor of glycogen synthase kinase 3 alpha;Inhibitor of glycogen synthase kinase 3 beta
Product Description
Product description: CHIR-98014 is an effective GSK-3Α and GSK-3Β inhibitor with IC50 values of 0.65 nM and 0.58 NM respectively. GSK-3(glycogen synthase Kinase 3) is a serine/threonine protein kinase that plays a key role in many intracellular signaling pathways, including Cell Proliferation, migration, inflammation and immune response, glucose regulation and apoptosis. GSK-3 is reported to be abnormally expressed in a variety of diseases, including type 2 diabetes, Alzheimer’s Disease, inflammation, cancer and bipolar disorder. CHIR-98014 is an effective inhibitor of GSK-3 Α and GSK-3 β. In CHO-IR cells or primary rat hepatocytes expressing INSR, CHIR-98014 stimulated GS activity in a dose-dependent manner, 2-3 times higher than baseline level. Similarly, CHIR-98014 activates GS more than [1] in type I skeletal muscles from insulin-sensitive Lean Zucker rats and insulin-resistant ZDF rats. In mouse ES-D3 cells, CHIR-98014 significantly activates Wnt/beta-catenin signaling pathway by inhibiting GSK-3 after 48 and 72 hours of treatment. CHIR-98014(30 mg/kg) significantly reduced fasting hyperglycemia within 4 hours after Oral Administration, and improved glucose treatment during oral or intravenous administration in a mouse model with marked diabetes and insulin resistance (DB/DB) .
Product Application：
CHIR 98014 has been used for the generation of small molecules neural progenitor cells and differentiation towards motor neurons. It has also been used as a Wnt/β-catenin pharmacological agonist in the cell-conditioned medium to perform chromatin immunoprecipitation (ChIP) studies in HT22 neurons.
1.Eldar-Finkelman H, Schreyer SA, Shinohara MM, LeBoeuf RC, Krebs EG. (1999) Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice.. Diabetes, 48 (8):(1662-6). [PMID:10426388][10.1021/op500134e]
2.Nikoulina SE, Ciaraldi TP, Mudaliar S, Mohideen P, Carter L, Henry RR. (2000) Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.. Diabetes, 49 (2):(263-71). [PMID:10868943][10.1021/op500134e]
3.Ring DB, Johnson KW, Henriksen EJ, Nuss JM, Goff D, Kinnick TR, Ma ST, Reeder JW, Samuels I, Slabiak T et al.. (2003) Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo.. Diabetes, 52 (3):(588-95). [PMID:12606497][10.1021/op500134e]
4.Cai Z, Zhao Y, Zhao B. (2012) Roles of glycogen synthase kinase 3 in Alzheimer's disease.. Curr Alzheimer Res, 9 (7):(864-79). [PMID:22272620][10.1021/op500134e]
5.Hurtado DE, Molina-Porcel L, Carroll JC, Macdonald C, Aboagye AK, Trojanowski JQ, Lee VM. (2012) Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease.. J Neurosci, 32 (21):(7392-402). [PMID:22623685][10.1021/op500134e]
6.Takashima A, Noguchi K, Sato K, Hoshino T, Imahori K. (1993) Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity.. Proc Natl Acad Sci USA, 90 (16):(7789-93). [PMID:8356085][10.1021/op500134e]
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