Highly Selective GSK-3 Inhibitor for iPS Cell Reprogramming and Organoid Culture
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CHIR 99021 [C4010] is a small-molecule inhibitor with high specificity for glycogen synthase kinase 3 (GSK-3), available in a cell culture grade that has been tested for endotoxin and mycoplasma contamination. GSK-3 regulates multiple signaling pathways in a context-dependent manner, including glycogen and protein synthesis, cell death and survival,¹) mRNA methylation,²) differentiation within the colonic secretory niche,³) and cell proliferation via the canonical Wnt pathway. Inhibition of GSK-3 stabilizes β-catenin, activating Wnt target genes and promoting long-term self-renewal. This involves suppression of Tcf3, a transcriptional repressor of pluripotency factors such as Oct4, Sox2, and Nanog.⁴,⁵) Accordingly, CHIR 99021 is widely used in chemical reprogramming cocktails for iPSC generation and in organoid culture systems where Wnt activation is required.
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References
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- Glycogen synthase kinase-3 (GSK-3) activity regulates mRNA methylation in mouse embryonic stem cells
- K. J. Faulds, J. N. Egelston, L. J. Sedivy, M. K. Mitchell, S. Garimella, H. Kozlowski, A. D’Alessandro, K. C. Hansen, J. L. Balsbaugh, C. J. Phiel, J. Biol. Chem. 2018, 293, 10731.
- Reciprocal targeting of Hath1 and β-catenin by Wnt glycogen synthase kinase 3β in human colon cancer
- K. Tsuchiya, T. Nakamura, R. Okamoto, T. Kanai, M. Watanabe, Gastroenterology 2007, 132, 208.
- Wnt Pathway Regulation of Embryonic Stem Cell Self-Renewal
- B. J. Merrill, Cold Spring Harb. Perspect. Biol. 2012, 4, a007971.
- Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation
- J. Wray, T. Kalkan, S. Gomez-Lopez, D. Eckardt, A. Cook, R. Kemler, A. Smith, Nat. Cell Biol. 2011, 13, 838.
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Source
- TCI Product Highlights: www.tcichemicals.com/ID/en/product/tci-topics/ProductHighlights_20260525
- TCI product page C2943: tcichemicals.com/ID/en/p/C2943
For research and laboratory use only, not for human consumption.