| 名稱 | Ruxolitinib (S enantiomer) |
| 描述 | Ruxolitinib S enantiomer (INCB18424) is the S-enantiomer of Ruxolitinib. Ruxolitinib is the first potent, selective JAK1/2 inhibitor. |
| 細胞實驗 | Cell lines: Ba/F3 and HEL cells. Concentrations: 3 μM. Method: Cells are seeded at 2×103/well of white bottom 96-well plates,treated with INCB018424 from DMSO stocks (0.2% final DMSO concentration),and incubated for 48 hours at 37 ℃ in an atmosphere containing 5% CO2.Viability is measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting.Values are transformed to percent inhibition relative to vehicle control,and IC50 curves are fitted according to nonlinear regression analysis of the data using PRISM GraphPad. |
| 激酶實驗 | Recombinant proteins expressed with Sf21 cells and baculovirus vectors are purified with affinity chromatography. JAK kinase assay is done by a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with Ruxolitinib or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1 mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. IC50 is the INCB018424 concentration required for inhibition of 50% of the fluorescent signal. |
| 動物實驗 | Animal Models: JAK2V617F-driven mouse modelFormulation & . Dosages: 5% dimethyl acetamide,0.5% methylcellulose.180 mg/kg. Administration: Oral gavage |
| 體外活性 | INCB018424（180 mg/kg,口服,每天兩次）顯著減少JAK2V617F驅(qū)動的小鼠模型中脾腫大和炎性細胞因子的循環(huán)水平,并優(yōu)先消滅腫瘤細胞,顯著延長生存期,且未產(chǎn)生骨髓抑制或免疫抑制.上述小鼠在第22天存活率超過90％.15 mg Ruxolitinib處理骨髓纖維化患者,每天兩次,在48周時,28％患者的脾臟體積減少至少35％.Ruxolitinib組的患者整體生活質(zhì)量改善,與骨髓纖維化有關(guān)的癥狀減輕. |
| 體內(nèi)活性 | INCB018424在Ba/F3細胞中以劑量依賴性方式顯著增加細胞凋亡。INCB018424作用于Ba/F3細胞和HEL細胞,有效且選擇性抑制JAK2V617F介導(dǎo)的信號和增殖。INCB018424(64 nM) 導(dǎo)致Ba/F3細胞線粒體去極化增加一倍。INCB018424抑制正常供體和真性紅細胞增多癥患者提供的紅系祖細胞增殖,IC50分別為407 nM 和 223 nM。INCB018424表現(xiàn)出對紅系細胞集落形成的有效作用,IC50為67 nM。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 57 mg/mL (186 mM)
Ethanol : 57 mg/mL (186 mM)
H2O : 5 mg/mL (16.32 mM)
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| 關(guān)鍵字 | S-INCB18424 | Ruxolitinib | INCB 018424 | INCB-18424 | Ruxolitinib (S enantiomer) | INCB-018424 | Janus kinase | JAK | inhibit | INCB 18424 | Inhibitor |
| 相關(guān)產(chǎn)品 | JAK-IN-10 | Tofacitinib Citrate | Deucravacitinib | Gefitinib | Ruxolitinib | CEP-33779 | Baricitinib | Fedratinib | GSK 3 Inhibitor IX | Ruxolitinib phosphate | Ibrutinib | Delgocitinib |
| 相關(guān)庫 | 抑制劑庫 | 抗癌上市藥物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | FDA 上市激酶抑制劑庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |