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Chemical Structure| 252917-06-9 Chemical Structure| 252917-06-9

Structure of CHIR 99021
CAS No.: 252917-06-9

Chemical Structure| 252917-06-9

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Laduviglusib (CHIR-99021) is an effective, selective, and orally active GSK-3α/β inhibitor used as an auxiliary agent in cell therapy.

Synonyms: CT99021; Laduviglusib

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Product Citations

Product Citations

Huang, Herman ; Park, Sangsoon ; Ross, Ines ; Moreno, Joseph ; Khyeam, Sheamin ; Simmons, Jacquelyn , et al.

Abstract: Cardiac regeneration in newborn rodents depends on the ability of pre-existing cardiomyocytes to proliferate and divide. This capacity is lost within the first week of postnatal development when these cells rapidly switch from hyperplasia to hypertrophy, withdraw from the , become binucleated, and increase in size. How these dynamic changes in cell size and nucleation impact cardiomyocyte proliferative potential is not well understood. In this study, we innovate the application of a commercially available digital holographic imaging microscope, the Holomonitor M4, to evaluate the proliferative responses of mononucleated and binucleated cardiomyocytes after CHIR99021 treatment, a model proliferative stimulus. This system enables long-term label-free quantitative tracking of primary cardiomyocyte dynamics in real-time with single-cell resolution. Our results confirm that chemical inhibition of glycogen synthase kinase 3 with CHIR99021 promotes complete cell division of both mononucleated and binucleated cardiomyocytes with high frequency. Quantitative tracking of cardiomyocyte volume dynamics during these proliferative events revealed that both mononucleated and binucleated cardiomyocytes reach a similar size-increase threshold prior to attempted cell division. Binucleated cardiomyocytes attempt to divide with lower frequency than mononucleated cardiomyocytes, which may be associated with inadequate increases in cell size. By defining the interrelationship between cardiomyocyte size, nucleation, and control, we may better understand the cellular mechanisms that drive the loss of mammalian cardiac regenerative capacity after birth.

Keywords: Neonatal rat ; Heart ; Cardiomyocyte ; Cell division ; Nucleation ; ; Digital holographic imaging

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Product Details of CHIR 99021

CAS No. :252917-06-9
Formula : C22H18Cl2N8
M.W : 465.34
SMILES Code : N#CC1=CN=C(NCCNC2=NC=C(C3=NC=C(C)N3)C(C4=CC=C(Cl)C=C4Cl)=N2)C=C1
Synonyms :
CT99021; Laduviglusib
MDL No. :MFCD11846251
InChI Key :AQGNHMOJWBZFQQ-UHFFFAOYSA-N
Pubchem ID :9956119

Safety of CHIR 99021

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of CHIR 99021

PI3K-AKT
Hedgehog

Isoform Comparison

Biological Activity

Target
  • GSK-3α

    GSK-3α, IC50:10 nM

  • GSK-3β

    GSK-3β, IC50:6.7 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Human induced pluripotent stem cells (hiPSCs) 8 μM 3 days By activating the Wnt signaling pathway, hiPSCs were induced to differentiate into cardiac lateral plate mesoderm cells (hiCLPM). PMC11062615
Lgr5+ intestinal stem cells 10 μM 7 days Maintain self-renewal and proliferation of Lgr5+ intestinal stem cells PMC6120946
HEK293T cells 5 or 10 μM Activate Wnt/β-catenin signaling to a level similar to Wnt plus R-spondin1 PMC6120946
B cells 10 µM 48 h Induced IL-10+ Bregs and suppressed TNF-α expression PMC11638867
Primary murine colonic epithelial cells 2.5 μM 48 h To investigate the impact of Wnt signaling on intracellular Ca2+ oscillation patterns, results showed that CHIR-99021 significantly increased Ca2+ spike frequency and decreased pulse width PMC8599644

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.21mL

10.74mL

2.15mL

1.07mL

21.49mL

4.30mL

2.15mL

References

[1]Martinez A, Castro A, et al. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 2002 Jul;22(4):373-84.

[2]Bennett CN, Ross SE, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002 Aug 23;277(34):30998-1004. Epub 2002 Jun 7.

[3]Ring DB, Johnson KW, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.

[4]Lian X, Zhang J, et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. 2013 Jan;8(1):162-75.

[5]Tian E, Sun G, et al. Small-Molecule-Based Lineage Reprogramming Creates Functional Astrocytes. Cell Rep. 2016 Jul 19;16(3):781-92.

[6]Ying QL, Wray J, et al. The ground state of embryonic stem cell self-renewal. Nature. 2008 May 22;453(7194):519-23.

[7]CHIR99021 attenuates mood-related behaviors in lithium responsive and non responsive

[8]Ring DB, Johnson KW, Henriksen EJ, Nuss JM, Goff D, Kinnick TR, Ma ST, Reeder JW, Samuels I, Slabiak T, Wagman AS, Hammond ME, Harrison SD. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95. doi: 10.2337/diabetes.52.3.588. PMID: 12606497.

[9]Lian X, Zhang J, Azarin SM, Zhu K, Hazeltine LB, Bao X, Hsiao C, Kamp TJ, Palecek SP. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. 2013 Jan;8(1):162-75. doi: 10.1038/nprot.2012.150. Epub 2012 Dec 20. PMID: 23257984; PMCID: PMC3612968.

[10]Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):E1848-57. doi: 10.1073/pnas.1200250109. Epub 2012 May 29. PMID: 22645348; PMCID: PMC3390875.

[11]Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A. The ground state of embryonic stem cell self-renewal. Nature. 2008 May 22;453(7194):519-23. doi: 10.1038/nature06968. PMID: 18497825; PMCID: PMC5328678.

 

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