| CAS |
No.941678-49-5 |
| 中文名称 |
鲁索利替尼(10mM in DMSO,无菌） |
| 英文名称 |
Ruxolitinib(10mM in DMSO，Sterile） |
| 分子式 |
C17H18N6 |
| 分子量 |
306.37 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 运输条件 |
冷冻运输 |
| 靶点 |
Janus kinase (JAK) |
| 通路 |
JAK/STAT Signaling |
| 背景说明 |
Ruxolitinib 是有效，选择性的 JAK1/2 抑制剂。 |
| 生物活性 |
Ruxolitinib (INCB18424) is a potent and selective JAK1/2 inhibitor with IC50s of 3.3 nM and 2.8 nM in cell-free assays， and has 130-fold selectivity for JAK1/2 over JAK3. Ruxolitinib induces autophagy and kills tumor cells through toxic mitophagy.[1-3] |
| In Vitro |
Ruxolitinib 有效且选择性地抑制 JAK2V617F 介导的信号传导和增殖，以剂量依赖性方式显著增加细胞凋亡，并且在 64 nM 时导致 Ba/F3 细胞中具有去极化线粒体的细胞加倍。Ruxolitinib 显示出显著的抗红细胞作用集落形成，IC50 为 67 nM，并抑制正常供体和真性红细胞增多症患者红细胞祖细胞的增殖，IC50 值分别为 407 nM 和 223 nM[1]。 |
| In Vivo |
Ruxolitinib (180 mg/kg，口服，每天两次) 导致第 22 天时的存活率超过 90%，并显著降低脾肿大和炎症细胞因子的循环水平，并优先消除肿瘤细胞，从而显著延长存活时间，而无骨髓抑制或JAK2V617F 驱动的小鼠模型中的免疫抑制作用[1]。在 Ruxolitinib 组中，41.9% 的患者达到主要终点，而安慰剂组为 0.7% 在骨髓纤维化的双盲试验中。Ruxolitinib 可维持脾脏体积减少，总症状评分改善 50% 或更多[2]。 |
| 细胞实验 |
Cells are seeded at 2×103/well of white bottom 96-well plates， treated with Ruxolitinib (INCB018424) from DMSO stocks (0.2% final DMSO concentration)， and incubated for 48 hours at 37°C with 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. |
| 动物实验 |
Mice are fed standard rodent chow and provided with water ad libitum. Ba/F3-JAK2V617F cells (105?per mouse) are inoculated intravenously into 6- to 8-week-old female BALB/c mice. Survival is monitored daily， and moribund mice are humanely killed and considered deceased at time of death. Treatment with vehicle (5% dimethyl acetamide， 0.5% methocellulose) or Ruxolitinib (INCB018424) begin within 24 hours of cell inoculation， twice daily by oral gavage. Hematologic parameters are measured using a Bayer Advia120 analyzed， and statistical significance is determined using Dunnett testing. |
| 激酶实验 |
Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use 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; 1mM)， and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC50) is calculated as INCB018424 concentration required for inhibition of 50% of the fluorescent signal. |
| 数据来源文献 |
[1]. Quintas-Cardama A， et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood， 2010， 115(15)， 3109-3117.
[2]. Verstovsek S， et al. A double-blind， placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med， 2012， 366(9)， 799-807.
[3]. Tavallai M， et al. Rationally Repurposing Ruxolitinib (Jakafi (?)) as a Solid Tumor Therapeutic.Front Oncol.?2016 Jun 13;6:142. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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