CHIR-99021 (CT99021)

Short Summary : GSK-3 inhibitor, Cell-permeable, ATP-competitive

Category : Stem Cell|GSK-3

Purity : 0.9873

CAS Number : 252917-06-9

Formula : C22H18Cl2N8

Molecular Weight : 465.34

SMILE : N#CC1=CC=C(NCCNC2=NC=C(C3=NC=C(C)N3)C(C4=CC=C(Cl)C=C4Cl)=N2)N=C1

Solubility : >23.3mg/mL in DMSO

Storage : Store at 4°C

Description : CHIR-99021 is a highly specific glycogen synthase kinase-3 (GSK-3) inhibitor which can inhibit both isoforms with IC50 of 10 nM (GSK-3) and 6.7 nM (GSK-3).
CHIR-99021 was proved to promote self-renewal and maintain pluripotency of both B6 and BALB/c ES cells via stabilizing the downstream effectors like c-Myc and -catenin[1]. In J1 mESC cells, CHIR-99021 played an important role in maintaining the colony morphology as well as the self-renewal when combined with leukemia inhibitory factor (LIF). CHIR-99021 has shown to regulate multiple signaling pathways which involve Wnt/-catenin, TGF-, Nodal and MAPK, and the expression of epigenetic regulatory genes like Dnmt3l[2].
CHIR-99021 has been demonstrated to promote DN3 thymocytes proliferation and differentiation in the absence of pre-TCR signaling, Notch1 signaling or CXCL12[3]. However, study has also found that higher concentration (10 M but not 1 M or 3 M) of CHIR99021 might selectively inhibit differentiation by activating IL-7 signaling pathway[3].
References:
1. Ye S1, 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.
2. Wu Y1, 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
3. PLoS One. 2013;8(3):e58501. doi: 10.1371/journal.pone.0058501. Epub 2013 Mar 20. Schroeder JH1, Bell LS, Janas ML, Turner M. Pharmacological inhibition of glycogen synthase kinase 3 regulates T cell development in vitro. PLoS One. 2013;8(3):e58501.

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