Stemolecule™ CHIR99021

04-0004 / 04-0004-10 / 04-0004-02

Brand: Stemgent™

Purchase product: USA Store

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The aminopyrimidine CHIR99021 is the most selective inhibitor of glycogen synthase kinase 3 β (GSK-3β) reported to date^1,2. 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.

Specifications

Product Name: Stemolecule CHIR99021

Catalog Number: 04-0004

Size

• 2 mg (Cat. No. 04-0004)
• 10 mg (Cat. No. 04-0004-10)
• 2 mg in 10 mM DMSO solution (Cat. No. 04-0004-02)

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

Chemical Formula: C₂₂H₁₈Cl₂N₈

Molecular Weight: 465.34

CAS Number: 252917-06-9

Purity: Greater than 95 % by HPLC analysis

Formulation: Off-white solid

Solubility: 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. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C. The effect of storage of stock solutions should be verified for each application.

Quality Control: 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.

References

1. Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., and Brivanlou, A.H. 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 (2004).
2. 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 (2004).
3. Ying, Q.L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., and Smith, A. The ground state of embryonic stem cell self renewal. Nature 453: 519-523 (2008).
4. 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. 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 (2004).

Additional Publications

• Yoo J; La Y; Lee EJ; Choi J-J; Oh J; Thang NX; Hong K. ATP-Dependent chromatin remodeler CHD9 controls the proliferation of embryonic stem cells in a cell culture condition-dependent manner. Biology 9:428 (2020).
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• Pereiro X; Miltner AM; La Torre A; Vecino E. Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells. Cells 9:1759 (2020).
• Shi G. Ddx56 maintains proliferation of mouse embryonic stem cells via ribosome assembly and interaction with the Oct4/Sox2 complex. Stem Cell Res Therap 301:314 (2020).
• Wang S-H; Wang X-P. Generation of an induced pluripotent stem cell (iPSC) line (THSJTUi001-A) from a Wilson's disease patient harboring a homozygous Arg778Leu mutation in ATP7B gene. Stem Cell Res 49:102050 (2020).
• Wang T; Li J; Xiao Y; Fu B; Wang P; Bai X; Cai G; Chen X; Li Q. Generation of induced pluripotent stem cell PLAFMCi002-A derived from peripheral blood mononuclear cells of polycystic kidney disease patient with PKD1 mutation. Stem Cell Res 49:102039 (2020).
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• Kim M; Hwang S-U; Yoon JD; Jeong YW; Kim E; Hyun S-H. Optimized Approaches for the Induction of Putative Canine Induced Pluripotent Stem Cells from Old Fibroblasts Using Synthetic RNAs. Animals 10:1848 (2020).
• Branca MA; Dias TP Cotovio JP; Rodrigues CAV; Fernandes TG; Cabra; JMS; Diogo MM. 3D Microwell Platform for Cardiomyocyte Differentiation of Human Pluripotent Stem Cells. Methods Mol Biol doi.org/10.1007/7651_2020_336: (2020).
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• Leitner D; Ramamoorthy M; Dejosez M; Zwaka TP. Immature mDA Neurons Ameliorate Motor Deficits in a 6-OHDA Parkinson's Disease Mouse Model and are Functional after Cryopreservation. Stem Cell Res in press:doi.org/10.1016/j.scr.2019.101617 (2019).
• Atmanli A; Hu D; Deiman FE; van de Vrugt AM; Black III LD; Domian IJ. Multiplex Live Single-Cell Transcriptional Analysis Demarcates Cellular Functional Heterogeneity. eLIFE 8:e49599 (2019).
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• Leibel SL; Winquist A; Tseu I; Wang J; Luo D; Shojaie S; Nathan N; Snyder E; Post M. Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy. Sci Rep 9:13450 (2019).
• LeRoy G; Oksuz O; Descostes D; Aoi Y; Ganai RA; Ortabozkoyun Kara H; Yu R-R; Lee C-H; Stafford J; Shilatifard A; Reinberg D. LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription in differentiated cells. Sci Advances 5:eaay3068 (2019).
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• Kuroda T; Yasuda S; Tachi S; Matsuyama S; Kusakawa S; Tano K; Miura T; Matsuyama A; Soto Y. SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation. Nature Commun 10:2175 (2019).
• Sattler K; El-Battrawy I; Zhao Z; Schrottenberg C; Yücel G; Lan H; Li X; Lang S; Zimmermann W-H; Cyganek L Utikal J; Wieland T; Ravens R; Bieback K; Borggrefe M; Zhou X; Akin I. Serum of patients with acute myocardial infarction prevents inflammation in iPSC-cardiomyocytes. Sci Rep 9:5651 (2019).
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• Zhang Y; Zhang Y; Li M; Mend F; Yu Z; Chen Y; Cui G. Combination of SB431542, CHIR99021 and PD0325901 has a synergic effect on abrogating valproic acid‑induced epithelial‑mesenchymal transition and stemness in HeLa, 5637 and SCC‑15 cells. Oncol Rep In Press:https://doi.org/10.3892/or.2019.7088 (2019).
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• Schlick SF. Fibroblast-Cardiomyocyte Cross-Talk in Heart Muscle Formation and Function. Ph.D. Thesis, Georg-August University Göttingen :   (2018).
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• Winston TS; Suddhapas K; Wang C; Ramos R; Soman P; Ma Z. Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells. Stem Cells Int Article ID: 5654324:11 pages (2019).
• van Rhijn, J-R. The role of FOXP2 in striatal circuitry. Ph.D. Thesis, Radboud University Nijmegen : (2019).
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• Coley LW. The Genetic and Epigenetic Effects of Pre-Treatment with the Small Molecule Inhibitors CHIR99021, PD0325901, and NuP0178 on Bovine Fetal Fibroblast Cells. Ph.D. Thesis, Louisiana State University : (2019).
• Scavuzzo MA; Chmielowiec J; Yang D; Wamble K; Chaboub LS; Duraine L; Tepe B; Glasgow SM; Arenkiel BR; Brou C; Deneen B; Borowiak M; . Pancreatic Cell Fate Determination Relies on Notch Ligand Trafficking by NFIA. Cell Reports 25:3811-3827.e7 (2018).
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