CHIR-98014

製品コードS2745 バッチS274502

印刷

化学情報

Chemical Structure Synonyms CT98014 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H17Cl2N9O2
分子量 486.31 CAS No. 252935-94-7
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 8 mg/mL (16.45 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 CHIR-98014 (CT98014) is a potent GSK-3α/β inhibitor with IC50 of 0.65 nM/0.58 nM in cell-free assays, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2.
in vitro CHIR-98014 inhibits human GSK-3β with Ki of 0.87 nM. This compound is very effective in preventing murine and rat GSK-3. Although it acts as a simple competitive inhibitor of ATP binding, it displays from 500-fold to >1000-fold selectivity for GSK-3 versus 20 other protein kinases including Cdc2, ERK2, Tie-2 and KDR. This inhibitor prevents Cdc2 with IC50 of 3.7 μM. However, it reveals similar potency against the highly homologous ɑ and β isoforms of GSK-3, it is noteworthy that it strongly discriminated between GSK-3 and its closest homologs CDC2 and ERK2. Exposure of insulin receptor-expressing CHO-IR cells or primary rat hepatocytes to increasing concentrations of this chemical results in a two- to three-fold stimulation of the GS activity ratio above basal. The concentrations giving rise to half-maximal GS stimulation (EC50) is 106 nM and 107 nM for CHO-IR and rat hepatocytes, respectively. [1]
in vivo GSK-3 inhibitor CHIR-98014 activates the GS activity ratio in isolated type I skeletal muscle from insulin-sensitive lean Zucker and from insulin-ressitant ZDF rats. Soleus muscle isolated from ZDF rats shows significant resistance to insulin for activation of GS but responded to 500 nM of this compound to the same extent (40% increase) as muscle from lean Zucker rats. Notably, GS activation by insulin plus this chemical is additive in muscle from lean Zucker rats and greater than additive in muscle from the ZDF rats. Total GS activity is not altered by either this inhibitor or insulin in these cells and muscles. Meanwhile, this compound does not influence the insulin dose-response in muscle from lean animals. The reduction in hyperglycemia and improved glucose disposal are not limited to db/db mice and ZDF rats, as similar results are observed with ob/ob mice, diet-induced diabetic C57BL/6 mice, and glucose-intolerant SHHF rats treated with this chemical. [1] Additionally, this compound decreases the phosphorylation (Ser396) of tau protein in the cortex and hippocampus of postnatal rats. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Kinase assays
Polypropylene 96-well plates are filled with 300 μL/well buffer (50 mM tris HCl, 10 mM MgCl2, 1 mM EGTA, 1 mM dithiothreitol, 25 mM β-glycerophosphate, 1 mM NaF, 0.01% BSA, pH 7.5) containing kinase, peptide substrate, and any activators. CHIR-98014 or controls are added in 3.5 μL of DMSO, followed by 50 μL of ATP stock to yield a final concentration of 1 μM ATP in all cell-free assays. After incubation, triplicate 100-μL aliquots are transferred to Combiplate eight plates containing 100 μL/well 50 μM ATP and 20 mM EDTA. After 1 hour, the wells are rinsed five times with PBS, filled with 200 μL of scintillation fluid, sealed, left 30 min, and counted in a scintillation counter. All steps are performed at room temperature.
細胞アッセイ 細胞株 CHO-IR cells
濃度 0.01-10 μM
反応時間 30 min
実験の流れ

CHO-IR cells expressing human insulin receptor are grown to 80% confluence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 106 cells/well in 2 mL of medium without fetal bovine serum. After 24 hours, medium is replaced with 1 mL of serum-free medium containing GSK-3 inhibitor CHIR 98014 or control (final DMSO concentration 0.1%) for 30 min at 37 °C. Cells are lysed by freeze/thaw in 50 mM tris (pH 7.8) containing 1 mM EDTA, 1 mM DTT, 100 mM NaF, 1 mM phenylmethylsulfonyl fluoride, and 25 μg/mL leupeptin (buffer A) and centrifuged 15 min at 4 °C/14000 g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mM glucose-6-phosphate.
動物実験 動物モデル db/db mice with 8-9 weeks
投薬量 30 mg/kg
投与方法 Subcutaneously

参考

  • https://pubmed.ncbi.nlm.nih.gov/12606497/
  • https://pubmed.ncbi.nlm.nih.gov/17906685/

カスタマーフィードバック

Data from [Stem Cells Dev, 2013, 22, 1893-90]

Data from [Stem Cells Dev, 2013, 22, 1893-90]

Data from [Stem Cells Dev, 2013, 22, 1893-90]

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長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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