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The aminopyrimidine CHIR99021 is the most selective inhibitor of glycogen synthase kinase 3 beta (GSK-3β) reported to date1,2. Unlike other potent inhibitors of GSK-3, CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs3. Along with the elimination of differentiation-inducing signaling from mitogen-activated protein kinases, using CHIR99021 to block the activity of GSK-3β enables the self-renewal of embryonic stem cells4.
Also available: Stemolecule™ CHIR99021 in Solution (04-0004-02)
2 mg (Cat. No. 04-0004)
10 mg (Cat. No. 04-0004-10)
Greater than 95% by HPLC analysis
Reconstitute in DMSO to the desired concentration. For reconstitution instructions please reference product specifications sheet.
Storage and Stability
Store powder at 4°C protected from light. Following reconstitution, store aliquots at -20°C. Stock solutions are stable for 6 months when stored as directed.
The purity of CHIR99021 was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of CHIR99021 was tested on mouse embryonic stem cells.
- Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., and Brivanlou, A.H. (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10: 55-63.
- Besser, D. (2004) Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad 2/3. J Biol Chem 279: 45076-45084.
- Ying, Q.L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., and Smith, A. (2008) The ground state of embryonic stem cell self renewal. Nature 453: 519-523.
- Polychronopoulos, P., Magiatis, P., Skaltsounis, A.L., Myrianthopoulos, V., Mikros, E., Tarricone, A., Musacchio, A., Roe, S.M., Pearl, L., Leost, M., Greengard, P., and Meijer, L. (2004) Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem 47: 935-946.
- Xia N; Zhang P; Fang F; Wang Z; Rothstein M; Agulo B; Chiang R; Taylor J; Reijo Pera RA. "Transcriptional comparison of human induced and primary midbrain dopaminergic neurons." Scientific Reports. 6:20270. doi:10.1038/srep20270 (2016)
- Han Y-C, Lim Y; Duffieldl MD; Liu J; Manaph NPA; Yang M; Keating DJ; Zhou X-F. "Direct reprogramming of mouse fibroblasts to neural stem cells by small molecules." Stem Cells International 2016:4304916 (2016)
- Zhu S; Russ HA; Wang X; Zhang M; Ma T; Xu T; Tang S; Hebrok M; Deng S. "Human pancreatic beta-like cells converted from fibroblasts." Nature Commun 7:10080 (2016)
- Titmarsh DM; Glass NR; Mills RJ; Hidalgo A; Volvetang EJ; Porrello ER; Hudson JE; Cooper-White JJ. "Induction of human iPSC-derived cardiomyocyte proliferation revealed by combinatorial screening in high density microbioreactor arrays." Sci Rep 6:24637 (2016)
- Liu G. "No detection of potential cancer risk for free-viral reprogrammed stem cell-derived dopaminergic neurons from adult mice fibroblasts." J Stem Cell Res Ther 5:286 (2015)
- Fonoudi H; Ansari H; Abbasalizadeh S; Laruani MR; Kiani S; Hashemizadeh S; Zarchi AS; Bosman A; Blue GM; Pahlavan S; Perry M; Orr Y; Mayorchak Y; Vandenberg J; Talkhabi M; Winlaw SD; Harvey RP; Aghdami N; Baharvand H. "A universal and robust integrated platform for the scalable production of human coardiomhyocytes from pluripotent stem cells." Stem Cells Trans Med 4:1482 (2015)
- Yang J; Kaur K; Ong LL; Eisenberg CA; Eisenberg LM. "Inhibition of G9a histone methyltransferase converts bbone marrow mesenchymal stem cells to cardiac competent progenitors." Stem Cells International Article 270428 (2015) doi:10.1155/2015/270428
- Ren J; Briones V; Barbour S; Yu W; Han Y; Tarashima M; Muegge K. "The ATP binding site of the chromatin remodeling homolog LSH is required for nucleosome density and de novo DNA methylation at repeat sequences." Nucl Acids Res doi: 10.1093/nar/gku1371 (2015)
- DeRosa BA; Belle KC; Thomas BJ; Cukier HN; Pericak-Vance MA; Vance JM; Dykxhoom DM. "hVGAT-mCherry: A novel molecular tool for analysis of GABAergic neurons derived from human pluripotent stem cells." Mol Cell Neurosci 68:244 (2015)
- Tan H-K; Toh C-XDl Ma D; Yang B; Liu TM; Lu J; Wong C-W; Tan T-K; Li H; SYn C; Tan E-L; Lim B; Lim Y-P; Cook SA; Loh Y-H. "Human finger-prick induced pluripotent stem cells facilitate the development of stem cell banking." Stem Cells Trans Medicine 3:586 (2014)
- Ying, Q., Tai, C. Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state. Journal of Cell Science 126, 1093 – 1098.(2013)
- Youn H; Kim S-H; Choi KA; Kim S. "Characterization of Oct4-GFP spermatogonial stem cell line and its applicationo in the reprogramming studies." J Cell Biochem 114:920 (2013)
- Blauwkamp TA; Nigam S; Ardehali R; Weissman IL; Nusse R. Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors. Nature Communications 3:1070 (2012).
- Lian, X., Hsiao, C., Wilson, G, Zhu, K., Hazeltine, L.B., Azarin, S.M., Raval, K.K., Zhang, J., Kamp, T.J., and Palecek, S.P. (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA 109: E1848 (2012)
- Moraveji S-F; Attari F; Shahverdi A; Sepehri H; Farrokhi A; Hassani S; Fonoudi H; Aghdami N; Baharvand H. "Inhibition of glycogen synthase kinase-3 promotes efficient derivation of pluripotent stem cells from neonatal mouse testis." Human Reproduction 27:2312 (2012)
- Nagy, K., Sung, H-K., Zhang, P., Laflamme, S., Vincent, P, Agha-Mohammadi, S., Woltjen, K., Monetti, C., Michael, I. P., Smith, L. C., Nagy, A. Induced Pluripotent Stem Cell Lines Derive from Equine Fibroblasts. Stem Cell Reviews and Reports 7:693 (2011).
- Wang, B., Miyagoe-Suzuki, Y., Yada, E., Ito, N., Nishiyama, T., Nakamura, M., Ono, Y., Motohashi, N., Segawa, M., Masuda, S., Takeda, S. Reprogramming Efficiency and Quality of Induced Pluripotent Stem Cells (iPSCs) Generated from Muscle-derived Fibroblasts of MDX Mice at Different Ages. PLOS Currents Muscular Dystrophy. 2011 Oct 27 . Edition 1. doi: 10.1371/currents.RRN1274 .
- Mack, A., Kroboth, S., Rajesh, D., Wang, W. B. Generation of Induced Pluripotent Stem Cells from CD34+ Cells across Blood Drawn from Multiple Donors with Non-Integrating Episomal Vectors. PLoS One; 6(11): e27956.(2011)
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- Chiang P-M; Wong PC. "Differentiation of an embryonic stem cell to hemogenic endothelium by defined factors: Essential role of bone morphogenetic protein 4." Development 138: 2833-2843 (2011)
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