CHIR99021 explained

CHIR99021 is a chemical compound which acts as an inhibitor of the enzyme GSK-3.^[1] It has proved useful for applications in molecular biology involving the transformation of one cell type to another.^{[2] [3]}

A mixture of CHIR99021 and valproic acid (FX-322) is claimed to increase the proliferation of inner ear stem cells, potentially allowing regrowth of the hair cells which are important for hearing, and are lost through chronic exposure to loud noises or as part of the aging process.^{[4] [5] [6]}

See also

• SB-431542

Notes and References

1. Book: An WF, Germain AR, Bishop JA, Nag PP, Metkar S, Ketterman J, Walk M, Weiwer M, Liu X, Patnaik D, Zhang YL, Gale J, Zhao W, Kaya T, Barker D, Wagner FF, Holson EB, Dandapani S, Perez J, Munoz B, Palmer M, Pan JQ, Haggarty SJ, Schreiber SL . 6 . Discovery of Potent and Highly Selective Inhibitors of GSK3b . https://www.ncbi.nlm.nih.gov/books/NBK133436/ . Probe Reports from the NIH Molecular Libraries Program. . Bethesda (MD) . National Center for Biotechnology Information (US) . 16 April 2012 . 23658955 .
2. Singh VK, Kumar N, Kalsan M, Saini A, Chandra R . Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs) . Journal of Stem Cells . 10 . 1 . 43–62 . 2015 . 26665937 .
3. Takeda Y, Harada Y, Yoshikawa T, Dai P . Chemical compound-based direct reprogramming for future clinical applications . Bioscience Reports . 38 . 3 . June 2018 . 29739872 . 5938430 . 10.1042/BSR20171650 .
4. US . 2017226477 . Compositions and methods for epithelial stem cell expansion and culture . Karp JM, Yin X, Succi MD, Langer RS . Massachusetts Institute of Technology . The Brigham and Women's Hospital, Inc. . 10 August 2017 .
5. US . 11033546 . Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor . Loose C, McLean W, Harrison M, Jirousek MR . Frequency Therapeutics Inc. . 15 June 2021 .
6. McLean WJ, Yin X, Lu L, Lenz DR, McLean D, Langer R, Karp JM, Edge AS . 6 . Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells . en . Cell Reports . 18 . 8 . 1917–1929 . February 2017 . 28228258 . 5395286 . 10.1016/j.celrep.2017.01.066 .