CHIR 99021 trihydrochloride

• CAT Number: I002310
• CAS Number: 1782235-14-6
• Molecular Formula: C₂₂H₁₈Cl₂N₈. 3HCl
• Molecular Weight: 574.72
• Purity: ≥95%
• Target: GSK-3β
• Solubility: DMSO: ≥ 32 mg/mL
• Storage: 3 years -20C powder
• InChI: InChI=1S/C22H18Cl2N8.3ClH/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19;;;/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32);3*1H
• InChIKey: DSFVSCNMMZRCIA-UHFFFAOYSA-N
• SMILES: CC1=CNC(C(C(C2=CC=C(Cl)C=C2Cl)=N3)=CN=C3NCCNC4=NC=C(C#N)C=C4)=N1.[H]Cl.[H]Cl.[H]Cl

CHIR-99021 trihydrochloride (CT99021) is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; > 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases.target： GSK-3α/βIn vitro: CHIR 99021 treatment increases bafilomycin-induced protein levels of the autophagosome marker LC3-II in excess nutrient conditions. CHIR 99021 also increases AMPK activity (as indicated by an increase in protein levels of p-ACCSer79). [2]CHIR99021, which prevents Myc degradation, could increase CD71 expression in IL-2-maintained CTL. [4]In vivo: In ZDF rats, a single oral dose of CHIR 99021 rapidly lowered plasma glucose, with a maximal reduction of nearly 150 mg/dl 3–4 h after administration. It is noteworthy that in these diabetic rats, the higher dose of CHIR 99021 also reduced hyperglycemia before the oral glucose challenge. [1] Treatment of mice with the GSK3β inhibitor CHIR 99021 increases LC3-II protein levels and AMPK activity and decreases Akt activity in the mouse aorta, suggesting that targeting GSK3β may be a viable strategy to induce autophagy in vivo. [2] CHIR99021 (CHIR)-induced activation of Wnt/β-catenin signaling promotes self-renewal in mouse ESCs (mESCs). [3]

Reference

[1]. Ring DB et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
[2]. Weikel KA et al. Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells. Biosci Rep. 2016 Sep 16;36(5).
[3]. Ai Z et al. CHIR99021 enhances Klf4 Expression through β-Catenin Signaling and miR-7a Regulation in J1 Mouse Embryonic Stem Cells. PLoS One. 2016 Mar 3;11(3)
[4]. Preston GC et al. Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. EMBO J. 2015 Aug 4;34(15):2008-24.
[5]. Preston GC et al. Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. EMBO J. 2015 Aug 4;34(15):2008-24.