Highly Selective Cell-Culture-Grade GSK3 Inhibitor for iPS Cell Reprogramming and Organoid Culture

CHIR 99021 is a small-molecule inhibitor with high specificity for glycogen synthase kinase 3 (GSK-3). 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, through which its primary role in iPSC reprogramming is exerted. Specifically, inhibition of GSK-3 stabilizes β-catenin, resulting in activation of Wnt target genes and promotion of long-term self-renewal. Mechanistically, this involves suppression of T-cell factor 3 (Tcf3), itself a transcriptional repressor of key pluripotency factors such as Oct4, Sox2, and Nanog.^4,5) Accordingly, CHIR 99021 is widely used in chemical reprogramming cocktails for iPSC generation, as well as in organoid culture systems where Wnt activation is required.
We offer two grades of CHIR 99021: a general-use grade and a cell culture grade, the latter of which has been tested for endotoxin and mycoplasma contamination for your peace of mind.

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References

• 1) Identification of an antiapoptotic protein complex at death receptors
  • M. Sun, L. Song, Y. Li, T. Zhou, R. S. Jope, Cell Death Differ. 2008, 15, 1887.
• 2) 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.
• 3) 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.
• 4) Wnt Pathway Regulation of Embryonic Stem Cell Self-Renewal
  • B. J. Merrill, Cold Spring Harb. Perspect. Biol. 2012, 4, a007971.
• 5) 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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