CHIR99021 trihydrochloride

CHIR99021, CHIR-73911, also known as CT-99021, or CHIR-911, is an orally active and potent GSK3 inhibitor. CHIR-73911 exhibited GSK3 IC50 in the low nanomolar range and excellent selectivity. CHIR-73911 activates glycogen synthase in insulin receptorexpressing CHO-IR cells and primary rat hepatocytes.

Product information

CAS Number: 1782235-14-6

Molecular Weight: 574.72

Formula: C22H21Cl5N8

Related CAS Number:

252917-06-9 (free base)

1797989-42-4 (HCl)

2109414-84-6 (2HCl)

Chemical Name: 6-[(2-{[4-(2, 4-dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino}ethyl)amino]pyridine-3-carbonitrile trihydrochloride

Smiles: Cl.Cl.Cl.CC1=CNC(=N1)C1=CN=C(NCCNC2=CC=C(C=N2)C#N)N=C1C1=CC=C(Cl)C=C1Cl

InChiKey: DSFVSCNMMZRCIA-UHFFFAOYSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

CHIR99021 inhibits human GSK-3β with Ki values of 9.8 nM[1]. CHIR99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases. In the presence of CHIR99021 the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM CHIR99021 with an IC50 of 4.9 μM.

In Vivo:

In ZDF rats, a single oral dose of CHIR99021 (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration. CHIR99021 (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). CHIR99021 treatment significantly blocks crypt apoptosis and accumulation of p-H2AX+ cells, and improves crypt regeneration and villus height. CHIR99021 treatment increases Lgr5+ cell survival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h.

References:

1. Bock AS, Leigh ND, Bryda EC. Effect of Gsk3 inhibitor CHIR99021 on aneuploidy levels in rat embryonic stem cells. In Vitro Cell Dev Biol Anim. 2014 Jun;50(6):572-9. doi: 10.1007/s11626-014-9734-5. Epub 2014 Feb 12. PubMed PMID: 24519175; PubMed Central PMCID: PMC4062835.
2. Wu Y, Liu F, Liu Y, Liu X, Ai Z, Guo Z, Zhang Y. GSK3 inhibitors CHIR99021 and 6-bromoindirubin-3'-oxime inhibit microRNA maturation in mouse embryonic stem cells. Sci Rep. 2015 Mar 2;5:8666. doi: 10.1038/srep08666. PubMed PMID: 25727520; PubMed Central PMCID: PMC4345320.
3. Wu Y, Ai Z, Yao K, Cao L, Du J, Shi X, Guo Z, Zhang Y. CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding RNA expression. Exp Cell Res. 2013 Oct 15;319(17):2684-99. doi: 10.1016/j.yexcr.2013.08.027. Epub 2013 Sep 7. PubMed PMID: 24021571.
4. Ye S, Tan L, Yang R, Fang B, Qu S, Schulze EN, Song H, Ying Q, Li P. Pleiotropy of glycogen synthase kinase-3 inhibition by CHIR99021 promotes self-renewal of embryonic stem cells from refractory mouse strains. PLoS One. 2012;7(4):e35892. doi: 10.1371/journal.pone.0035892. Epub 2012 Apr 23. PubMed PMID: 22540008; PubMed Central PMCID: PMC3335080.

Products are for research use only. Not for human use.