CHIR 99021 trihydrochloride
CHIR 99021 trihydrochloride is hydrochloride of CHIR 99021, which inhibits GSK-3α and GSK-3β with IC50 values of 10 nM and 6.7 nM. GSK-3 is a serine/threonine kinase, responsible for phosphorylating either the serine or threonine residues of its substrates. This phosphorylation process is involved in various key biological processes, including gene transcription, protein synthesis, cell signaling, cellular transport, proliferation, apoptosis, intracellular communication and glucose regulation.
References:
1. Ring DB, Johnson KW, Henriksen EJ, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes, 2003, 52(3): 588-595.
2. Pandey MK, DeGrado TR. Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics, 2016, 6(4): 571-593.
3. Mussmann R, Geese M, Harder F, et al. Inhibition of GSK3 promotes replication and survival of pancreatic beta cells. Journal of Biological Chemistry, 2007, 282(16): 12030-12037.
| Physical Appearance | Off White solid |
| Storage | Store at -20°C |
| M.Wt | 574.72 |
| Formula | C22H18Cl2N8·3HCl |
| Solubility | insoluble in EtOH; ≥21.87 mg/mL in DMSO; ≥32.45 mg/mL in H2O |
| Chemical Name | (Z)-6-((2-((E)-(4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2(1H)-ylidene)amino)ethyl)imino)-1,6-dihydropyridine-3-carbonitrile trihydrochloride |
| SDF | Download SDF |
| Canonical SMILES | CC(N1)=CN=C1C(C(C2=C(Cl)C=C(Cl)C=C2)=N/3)=CNC3=N/CC/N=C4C=CC(C#N)=CN/4.Cl.Cl.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[3] | |
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Cell lines |
INS-1E cells |
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Reaction Conditions |
0 ~ 20 μM CHIR 99021 for 24 h incubation |
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Applications |
CHIR 99021 increased the rate of proliferation of INS-1E cells in a dose-dependent manner, with the rate of proliferation reaching a maximum in the presence of 2.5 ~ 10 μM CHIR 99021. Moreover, CHIR 99021 also dose-dependently counteracted INS-1E cell death induced by high glucose and high palmitate. |
| Animal experiment:[1] | |
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Animal models |
Male ZDF rats with type 2 diabetes |
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Dosage form |
16, 30 or 48 mg/kg Orally |
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Applications |
In ZDF rats with type 2 diabetes, a single oral dose of CHIR 99021 at 30 mg/kg rapidly lowered plasma glucose, with a maximal reduction of nearly 150 mg/dl 3 ~ 4 hours after administration, while plasma insulin remained at or below control levels. Moreover, oral administration of CHIR 99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats substantially improved glucose tolerance, with 14% and 33% reduction in plasma glucose. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Ring DB, Johnson KW, Henriksen EJ, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes, 2003, 52(3): 588-595. 2. Pandey MK, DeGrado TR. Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics, 2016, 6(4): 571-593. 3. Mussmann R, Geese M, Harder F, et al. Inhibition of GSK3 promotes replication and survival of pancreatic beta cells. Journal of Biological Chemistry, 2007, 282(16): 12030-12037. |
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Quality Control & MSDS
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Chemical structure
