CHIR99021, Free Base, >99% C-6556
M.W. 465.34 C
Storage: Store at or below -20 ºC.
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
• CHIR99021 specifically inhibits glycogen synthase kinase-3β
(GSK3β, IC50 = 5 nm) and GSK3α (IC50 = 10 nm), inhibits
preadipocyte differentiation (IC50 = 0.3 µM), possibly by
blocking induction of C/EBPα and PPARγ, and mimics Wnt
signaling in 3T3-L1 preadipocytes. Bennett, C.N. et al.,
“Regulation of Wnt signaling during adipogenesis.”
J. Biol. Chem. 277: 30998-31004 (2002).
• CHIR99021 showed highly selective inhibition of GSK-3α and
GSK-3β, with IC50s of 10 nM and 6.7 nM, respectively. It showed
i of 9.8 nM for GSK-3β. However, it exhibited an IC50 of
8800 nM for CDC2. CHIR99021 activates glycogen synthase
in CHO-IR cells with EC
50 of 763 nM. ZDF rats display insulin
resistance, glucose intolerance, and mild hyperglycemia. In these
rats, a single oral dose of CHIR 99021 rapidly reduced plasma
glucose while plasma insulin remained at or below control
levels. ZDF rats treated with CHIR 99021 showed significantly
improved glucose tolerance with no significant differences
in plasma insulin levels compared with control animals.
Ring, D.B. et al., “Selective glycogen synthase kinase 3 inhibitors
potentiate insulin activation of glucose transport and utilization
in vitro and in vivo.” J. Biol. Chem. 277: 30998-31004 (2002).
Diabetes 52: 588-595 (2003).
• Alsterpaullone, kenpaullone, SB 214763, and SB 415286 not
only inhibited GSK-3 potently but also blocked CDKs. In
contrast, CHIR99021 showed 350-fold selectivity toward GSK-3
compared to CDKs. GSK-3 is an important intermediate in the
pathway from the insulin receptor to the Thymine-rich Insulin
Response Element (TIRE). Regulation of gene transcription by
insulin totally depends on GSK-3 inhibition. Finlay, D. et al.,
“Glycogen synthase kinase-3 regulates IGFBP-1 gene
transcription through the thymine-rich insulin response element.”
BMC Mol. Biol. 5: 15 (2004).
• CHIR99021 induced osteoblastogenesis, increased mineralization,
and inhibited adipogenesis in ST2 cells. Bennett C.N. et al.,
“Regulation of osteoblastogenesis and bone mass by Wnt10b.”
Proc. Natl. Acad. Sci. USA 102: 3324-3329 (2005).
• GSK-3 is a regulator of pancreatic beta cell replication and
survival, and the GSK3 inhibitor CHIR99021 increased the rate of
INS-1E beta cell replication. Mussmann, R. et al., “Inhibition of
GSK3 promotes replication and survival of pancreatic beta cells.”
J. Biol. Chem. 282: 12030-12037 (2007).
• Sold for laboratory or manufacturing purposes only; not for
human, veterinary, food, or household use.
• This product is offered for R&D use in accordance with (i) 35
USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese
Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent
Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K.
Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6)
and other common law exemptions of Canadian patent law; (vi)
Section 68B of the Patents Act of 1953 in New Zealand together
with the amendment of same by the Statutes Amendment Bill of
2002; (vii) such related legislation and/or case law as may be or
become applicable in the aforementioned countries; and (viii) such
similar laws and rules as may apply in various other countries.
• Not available in some countries; not available to some institutions;
not available for some uses.