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受注：045-509-1970 |
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化学情報
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Synonyms | CT98014 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C20H17Cl2N9O2 |
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| 分子量 | 486.31 | CAS No. | 252935-94-7 | |
| Solubility (25°C)* | 体外 | DMSO | 8 mg/mL warmed with 50ºC water bath (16.45 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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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. |
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| in vitro | CHIR-98014 inhibits human GSK-3β with Ki of 0.87 nM. CHIR-98014 is very effective in preventing murine and rat GSK-3. Although CHIR-98014 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. CHIR-98014 prevents Cdc2 with IC50 of 3.7 μM. However, CHIR 98014 reveals similar ptoency against the highly homologous ɑ and β isoforms of GSK-3, it is noteworthy that it stronly 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 inhibitor CHIR98014 results in a two- to three-fold stimulation of the GS activity ratio above basal. The concentrations of CHIR-98014 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 CHIR-98014 to the same extent (40% increase) as muscle from lean Zucker rats. Notably, GS activation by insulin plus CHIR-98014 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 CHIR-98014 or insulin in these cells and muscles. Meanwhile, CHIR-98014 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 CHIR-98014. [1] Additionally, CHIR-98014 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 | |
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| 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. |
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| 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
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カスタマーフィードバック
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Data from [Stem Cells Dev, 2013, 22, 1893-90]
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Data from [Stem Cells Dev, 2013, 22, 1893-90]
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Data from [Stem Cells Dev, 2013, 22, 1893-90]
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| CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F Translation Initiation Complex [ Adv Sci (Weinh), 2023, 10(12):e2206542] | PubMed: 36786012 |
| mTORC1 Mediates Biphasic Mechano-Response to Orchestrate Adhesion-Dependent Cell Growth and Anoikis Resistance [ Adv Sci (Weinh), 2023, e2307206.] | PubMed: 38041494 |
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| iPSC-derived exosomes promote angiogenesis in naturally aged mice [ Aging (Albany NY), 2023, 15(12):5854-5872] | PubMed: 37367945 |
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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