CHIR99021

CHIR99021 is a highly potent and selective small molecule inhibitor of glycogen synthase kinase 3 (GSK-3), with strong preference for the β isoform (GSK-3β) but also inhibits GSK-3α. It acts as an ATP-competitive inhibitor with IC50 values of approximately 6.7 nM for GSK‑3β and 10 nM for GSK‑3α[1][5][8]. By inhibiting GSK‑3 activity, CHIR99021 activates the Wnt/β-catenin signaling pathway by preventing phosphorylation and degradation of β-catenin. This leads to stabilization and nuclear accumulation of β-catenin[2]. The compound is widely used in stem cell research to promote self-renewal and pluripotency in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), as well as to guide differentiation into specific lineages[1][2][8]. It has also been studied in regenerative medicine applications such as liver regeneration, cardiomyocyte differentiation, neuronal progenitor proliferation, bone tissue engineering, hair follicle formation, lung regeneration, corneal endothelial cell proliferation, and feather follicle growth[10]. The compound is not approved for therapeutic use in humans; it is primarily a research tool.

Brand names

Stemolecule CHIR99021

Other names

6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)-2-pyrimidinyl]amino]ethyl]amino]-3-pyridinecarbonitrile