CHIR99021 (≥98%,HPLC),casno:252917-06-9 (FandaChem)
CAS：252917-06-9
MF：C22H18Cl2N8
MW：465.34
Synonyms：
CHIR99021
CT 99021
GSK-3 Inhibitor XVI
CT99021
CHIR99021
CHIR 99021
CT-99021
CT 99021(CHIR 99021)
6-[2-[4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino]ethylamino]pyridine-3-carbonitrile

Properties
Boiling point：784.1±70.0°CDensity：1.48
Acidity coefficient(pKa)：11.92±0.10(Predicted)
HPLC:Shows Min >99% purity
Formulation：crystalline solid
Solubility: Soluble in DMSO at 25 mg/mL with warming; very poorly soluble in ethanol; very poorly soluble in water; maximum
solubility in plain water is estimated to be about 20-40 μM; buffers, serum, or other additives may increase or decrease the
aqueous solubility.
Storage：-20°C
Stability：≥ 2 years

Introduction
CHIR99021 (≥98%,HPLC),casno:252917-06-9 is a potent and selective inhibitor of glycogen synthase kinase-3β (GSK3β, IC50 = 5 nM) and GSK3α (IC50 = 10 nM)1.possibly by blocking induction of C/EBPα and PPARγ, and mimics Wnt signaling in 3T3-L1 preadipocytes. CHIR99021 activates glycogen synthase in CHO-IR cells with EC50 of 763 nM. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) with 350-fold selectivity toward GSK-3β compared to CDKs. Induces osteoblastogenesis, increases
mineralization and inhibits adipogenesis in ST2 cells2. Promotes replication and survival of pancreatic beta cells3. CHIR-99021
enhances differentiation and reduces proliferation of adult human olfactory epithelium neural precursors4. Cell permeable and active
in vivo.

In vitro study
CHIR99021 (≥98%,HPLC),casno:252917-06-9 inhibits human GSK-3β with Ki values of 9.8nM.CHIR-99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR-99021 specifically inhibits GSK3β(IC50=~5nM) and GSK3α(IC50=~10nM),with little effect on other kinases. In the presence of CHIR-99021 the viability of the ES-D3 cells is reduced by 24.7%at 2.5μM,56.3% at 5μM,61.9% at 7.5μM and 69.2% at 10μM CHIR-99021 with an IC50 of 4.9μM.

In vivo study
In ZDF rats, a single oral dose of CHIR99021,casno:252917-06-9 (16mg/kg or 48mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150mg/dl3-4h after administration.CHIR99021 (2mg/kg) given once,4h before irradiation, significantly improvs survival after 14.5Gy
abdominal irradiation.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 4h.

References
【1】 Lu, et. al. Neural Stem Cells Derived by Small Molecules Preserve Vision Trans Vis Sci Tech. 2013;2(1):1
【2】 Bennett et al. (2002), Regulation of Wnt signaling during adipogenesis; J. Biol. Chem., 277 30998
【3】 Bennett et al. (2005), Regulation of osteoblastogenesis and bone mass by Wnt10b; Proc. Natl. Acad. Sci. USA, 102 3324
【4】 Mussmann et al. (2007), Inhibition of GSK3 promotes replication and survival of pancreatic beta cells; J. Biol. Chem., 282
12030
【5】 Manceur et al. (2011), Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of
adult human olfactory epithelium neural precursors; Exp. Cell. Res., 317 2086
【6】 Takaoka et al. (2016), Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis Lung carcinoma 3LL
cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid; Cancer Sci., 107 644 [Focus Citation]