| 名稱 | Decernotinib |
| 描述 | Decernotinib (VRT-831509)(VX-509; VRT-831509) is a potent and selective Janus kinase 3 (JAK3) inhibitor with Ki of 2.5 nM; IC50 is 50-170 nM in cellular assays. |
| 細胞實驗 | Frozen purified human B cells atr thawed, washed, and resuspended in complete medium. Cells are plated onto a 96-well plate at a density of 2 × 105 cells/well. VX-509 is added, and plates are incubated for 30 minutes at 37°C, followed by stimulation with a combination of 10 ng/ml IL-4 and 1 μg/ml CD40L. DMSO alone is added to the top two rows, one of which is stimulated with IL-4 or CD40L (negative control) and the other of which served as a proliferation control. The plates are incubated at 37°C for 6 days. On day 6, cells are pulsed with [3H]thymidine for 7 hours and harvested onto filters for radioactive determination using a PerkinElmer-Wallace beta counter (1205 Betaplate Beta Liquid Scintillation Counter). Data are analyzed with Softmax pro software to generate an IC50 value.(Only for Reference) |
| 激酶實驗 | Kinase Activity Assays: The effect of VX-509 on JAK3 activity is assessed by measuring the residual kinase activity of the recombinantly expressed JAK3 kinase domain using a radiometric assay. The final concentrations of the components in the assay are as follows: 100 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM dithiothreitol (DTT), 0.01% BSA, 0.25 nM JAK3, 0.25 mg/ml polyE4Y, and 5 μM 33P-γ-ATP (200 μCi/μMol). A 10 mM stock solution of VX-509 is prepared in DMSO, from which additional dilutions are prepared. A substrate mixture (100 mM HEPES, 10 mM MgCl2, 0.5 mg/ml polyE4Y, and 10 μM 33P-γ-ATP) is added and mixed with VX-509 stock solution. The reaction is initiated by the addition of an enzyme mixture [100 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM DTT, 0.02% BSA, 0.5 nM JAK3]. After 15 minutes, the reaction was quenched with 20% trichloroacetic acid (TCA). The quenched reaction was transferred to the GF/B filter plates and washed three times with 5% TCA. Following the addition of Ultimate Gold scintillant (50 μl), the samples were counted in a Packard TopCount gamma counter (PerkinElmer). In this procedure, the radioactivity trapped is a measure of the residual JAK3 kinase activity. From the activity versus concentration of VX-509 titration curve, the Ki value was determined by fitting the data to an equation for competitive tight binding inhibition kinetics using Prism software. |
| 體外活性 | 在HT-2細胞中，Decernotinib抑制了IL-2刺激的HT-2 STAT-5磷酸化、人類T細胞爆發(fā)增殖和CD40L/IL-4誘導的B細胞增殖。[1] |
| 體內(nèi)活性 | 在大鼠膠原誘導性關(guān)節(jié)炎模型中，Decernotinib(50 mg/kg, 口服) 顯示出劑量依賴性地減少踝部腫脹和爪重，并改善爪部組織病理學評分。在小鼠草酰胺誘導的遲發(fā)型超敏反應(yīng)模型中，Decernotinib(50 mg/kg, 口服) 顯著抑制耳部水腫。[1] 在大鼠HvG模型中，Decernotinib(50 mg/kg, 口服) 以劑量依賴的方式抑制腘淋巴結(jié) (PLN) 增生。[2] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 72 mg/mL (183.5 mM), Sonication is recommended.
Ethanol : 16 mg/mL (40.78 mM), Sonication is recommended.
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| 關(guān)鍵字 | VX509 | VX 509 | VRT831509 | VRT 831509 | TyrosineKinases | Tyrosine Kinases | Tyk2 | Janus kinase | JAK3 | JAK2 | JAK1 | JAK | Inhibitor | inhibit | Decernotinib |
| 相關(guān)產(chǎn)品 | JAK-IN-10 | Fedratinib | Tofacitinib Citrate | Deucravacitinib | Gefitinib | RO8191 | TAK-901 | CEP-33779 | GSK 3 Inhibitor IX | Ruxolitinib phosphate | Delgocitinib | Ibrutinib |
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