Sigma-Aldrich Gsk-3 Inhibitor Xxix, Chir

Assay

≥95% (HPLC)

Quality Level

100

Form

powder

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

yellow

Solubility

DMSO: 25 mg/mL

Storage Temp.

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)

Inchi Key

MDZCSIDIPDZWKL-UHFFFAOYSA-N

General Description

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 Actions

Cell permeable: yesPrimary Target
GSK-3 α & βTarget IC₅₀: 650 and 580 pM for GSK-3&alphaTarget K_i: 870 pM for human GSK-3&beta

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Grigoryan, T., et Al. 2013.Proc. Natl. Acad. Sci. USA 110,18174.
Lian, X., et Al. 2012.Proc. Natl. Acad. Sci. USA 109,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.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany