CHIR99021

CHIR99021

Names
IUPAC name 6-((2-((4-(2,4-Dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-yl)amino)ethyl)amino)nicotinonitrile
Other names Laduviglusib [1]
Identifiers
CAS Number	252917-06-9  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:91091
ChEMBL	ChEMBL412142
ChemSpider	8131728
ECHA InfoCard	100.236.922
EC Number	809-015-4
IUPHAR/BPS	8014
KEGG	D12196
PubChem CID	9956119
UNII	234CMT4GK4  Y
CompTox Dashboard (EPA)	DTXSID90179931
InChI InChI=1S/C22H18Cl2N8/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32) Key: AQGNHMOJWBZFQQ-UHFFFAOYSA-N
SMILES N#CC1=CN=C(NCCNC2=NC=C(C3=NC(C)=CN3)C(C4=CC=C(Cl)C=C4Cl)=N2)C=C1
Properties
Chemical formula	C22H18Cl2N8
Molar mass	465.34 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

CHIR99021 is a chemical compound which acts as an inhibitor of the enzyme GSK-3. ^[2] It has proved useful for applications in molecular biology involving the transformation of one cell type to another. ^{[3] [4]}

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. ^{[5] [6] [7]}

The substance has been used as part of a chemical cocktail to turn old and senescent human cells back into young ones (as measured by transcriptomic age), without turning them all the way back into undifferentiated stem cells. ^[8]

See also

• SB-431542

References

1. "Laduviglusib". PubChem. Retrieved 2025-03-20.
2. An WF, Germain AR, Bishop JA, Nag PP, Metkar S, Ketterman J, et al. (16 April 2012). "Discovery of Potent and Highly Selective Inhibitors of GSK3b". Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US). PMID   23658955.
3. Singh VK, Kumar N, Kalsan M, Saini A, Chandra R (2015). "Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs)". Journal of Stem Cells. 10 (1): 43–62. PMID   26665937.
4. Takeda Y, Harada Y, Yoshikawa T, Dai P (June 2018). "Chemical compound-based direct reprogramming for future clinical applications". Bioscience Reports. 38 (3) BSR20171650. doi:10.1042/BSR20171650. PMC   5938430 . PMID   29739872.
5. US 2017226477,Karp JM, Yin X, Succi MD, Langer RS,"Compositions and methods for epithelial stem cell expansion and culture",published 10 August 2017, assigned to Massachusetts Institute of Technologyand The Brigham and Women's Hospital, Inc. 
6. US 11033546,Loose C, McLean W, Harrison M, Jirousek MR,"Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor",published 15 June 2021, assigned to Frequency Therapeutics Inc. 
7. McLean WJ, Yin X, Lu L, Lenz DR, McLean D, Langer R, et al. (February 2017). "Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells". Cell Reports. 18 (8): 1917–1929. doi:10.1016/j.celrep.2017.01.066. PMC   5395286 . PMID   28228258.
8. Yang JH, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, Tian X, Ibrahim N, Chen Z, Griffin PT, Arnold M, Li J, Martinez OA, Behn A, Rogers-Hammond R, Angeli S, Gladyshev VN, Sinclair DA (July 2023). "Chemically induced reprogramming to reverse cellular aging". Aging. 15 (13): 5966–5989. doi:10.18632/aging.204896. PMC   10373966 . PMID   37437248.