5.31167

GSK-3 Inhibitor XXIX, CHIR98014

• Sinônimo(s): GSK-3 Inhibitor XXIX, CHIR98014, N²-(2-(4-(2,4-Dichlorophenyl)-5-(1H-imidazol-1-yl)pyrimidin-2-ylamino)ethyl)-5-nitropyridine-2,6-diamine, N⁶-(2-((4-(2,4-Dichlorophenyl)-5-(1H-imidazol-1-yl)-2-pyrimidinyl)amino}ethyl)-3-nitro-2,6-pyridinediamine, CHIR-98014, CT-98014
• Fórmula empírica (Notação de Hill): C₂₀H₁₇Cl₂N₉O₂
• Número CAS: 252935-94-7
• Peso molecular: 486.31
• Número MDL: MFCD10565922
• Código UNSPSC: 12352200
• NACRES: NA.77

Propriedades

• Ensaio: ≥95% (HPLC)
• Nível de qualidade: 100
• forma: powder
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: yellow
• solubilidade: DMSO: 25 mg/mL
• temperatura de armazenamento: 2-8°C
• InChI: 1S/C20H17Cl2N9O2/c21-12-1-2-13(14(22)9-12)18-16(30-8-7-24-11-30)10-27-20(29-18)26-6-5-25-17-4-3-15(31(32)33)19(23)28-17/h1-4,7-11H,5-6H2,(H3,23,25,28)(H,26,27,29)
• chave InChI: MDZCSIDIPDZWKL-UHFFFAOYSA-N

Descrição

Descrição geral

A cell-permeable, highly potent, ATP-competitive, reversible inhibitor of both GSK-3α and β (IC₅₀ = 650 and 580 pM, respectively).

A cell-permeable, brain permeant aminopyrimidine compound that acts as a potent, ATP-competitive and reversible inhibitor of both GSK-3α and β (IC₅₀ = 650 and 580 pM, respectively; K_i = 870 pM for human GSK-3β) and significantly affects downstream effects of GSK-3. Displays excellent selectivity over closely related Cdc2 and Erk2 (IC₅₀ = 3.7 µM & >10 µM, respectively). Does not affect the activity of several other protein kinases studied. Acutely sensitizes glycogen synthase activity in isolated skeletal muscle from insulin-sensitive lean Zucker and insulin-resistant Zucker diabetic fatty (ZDF) rats and can also augment insulin-stimulated glucose uptake in ZDF rats. However, it does not affect the basal glucose uptake rate. Induces a significant reduction in fasting hyperglycemia in diabetic and insulin-resistant db/db mice (~30 mg/kg, s.c.). Reduces Tau phosphorylation (Ser396) in the cortex and hippocampus of postnatal rats. Also shown to activate Wnt/β-catenin signaling and direct the differentiation of human pluripotent stem cells into cardiomyocytes.

A cell-permeable, brain permeant aminopyrimidine compound that acts as a potent, ATP-competitive and reversible inhibitor of both GSK-3α and β (IC₅₀ = 650 and 580 pM, respectively; K_i = 870 pM for human GSK-3β) and significantly affects downstream effects of GSK-3. Displays excellent selectivity over closely related Cdc2 and Erk2 (IC₅₀ = 3.7 µM & >10 µM, respectively). Does not affect the activity of several other protein kinases studied. Acutely sensitizes glycogen synthase activity in isolated skeletal muscle from insulin-sensitive lean Zucker and insulin-resistant Zucker diabetic fatty (ZDF) rats and can also augment insulin-stimulated glucose uptake in ZDF rats. However, it does not affect the basal glucose uptake rate. Induces a significant reduction in fasting hyperglycemia in diabetic and insulin-resistant db/db mice (~30 mg/kg, s.c.). Reduces Tau phosphorylation (Ser396) in the cortex and hippocampus of postnatal rats. Also shown to activate Wnt/β-catenin signaling and direct the differentiation of human pluripotent stem cells into cardiomyocytes.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
GSK-3 α & β

Target IC₅₀: 650 and 580 pM for GSK-3&alpha

Target K_i: 870 pM for human GSK-3&beta

Advertência

Toxicity: Standard Handling (A)

Reconstituição

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Outras notas

Grigoryan, T., et al. 2013. Proc. Natl. Acad. Sci. USA110, 18174.
Lian, X., et al. 2012. Proc. Natl. Acad. Sci. USA109, E1848.
Selenica, M.L., et al. 2007. Br. J. Pharmacol.152, 959.
Ring, D.B., et al. 2003. Diabetes.52, 588.
Nikoulina, S.E., et al. 2002. Diabetes.51, 2190.

Informações legais

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable