GSK-3 Inhibitor XXIX, CHIR98014

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.

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

Toxicity: Standard Handling (A)

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

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.

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