5.31167

GSK-3 Inhibitor XXIX, CHIR98014

• Synonym(e): 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
• Empirische Formel (Hill-System): C₂₀H₁₇Cl₂N₉O₂
• CAS-Nummer: 252935-94-7
• Molekulargewicht: 486.31
• MDL-Nummer: MFCD10565922
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥95% (HPLC)
• Qualitätsniveau: 100
• Form: powder
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: yellow
• Löslichkeit: DMSO: 25 mg/mL
• Lagertemp.: 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)
• InChIKey: MDZCSIDIPDZWKL-UHFFFAOYSA-N

Beschreibung

Allgemeine Beschreibung

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.

Biochem./physiol. Wirkung

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

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

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

Sonstige Hinweise

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.

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable