Ruxolitinib (INCB18424)
(Synonyms: 芦可替尼; INCB18424) 目录号 : GC14191
Ruxolitinib (INCB18424)作为一种抑制剂，能够抑制Janus相关激酶(JAKs)JAK1和JAK2, IC50 分别为 3.3 nM 和 2.8 nM，Ruxolitinib介导对造血和免疫功能重要的若干细胞因子和生长因子信号。
Cas No.:941678-49-5
Sample solution is provided at 25 µL, 10mM.
Ruxolitinib (INCB18424), as an inhibitor, inhibits Janus-associated kinases (JAKs)JAK1 and JAK2 with IC50 values of 3.3 nM and 2.8 nM, respectively. Ruxolitinib mediates several cytokine and growth factor signaling important for hematopoietic and immune function[1-3].
Ruxolitinib (INCB18424) (500nM-50μM;30min) significantly inhibited the production of IL-6, TNF-α and MCP-1 as induced by A23817 and substance P in HMC1 cells[4]. Ruxolitinib(0-400nM; 3days) reduced the level of cytokine release in CAR-T cells[5].
Ruxolitinib (INCB18424) (30 mg/kg; p.o.; twice a day 14 days) treatment alleviated renal damage in UUO mice[6]. Ruxolitinib(twice daily by oral gavage; 2 weeks) treatment improves viability and splenomegaly in a JAK2V617F-driven model of malignant disease[3]. Treatment of Fancc-/- mice with ruxolitinib(45 mg/kg; i.p; 5 days/week) decreased anemia, enhanced granulocytosis, delayed clonal progression and prolonged survival during repeated emergency granulopoiesis episodes[7].
References:
[1]. Becker H, Engelhardt M, et,al. Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16. PMID: 24756798.
[2]. Ajayi S, Becker H, et,al. Ruxolitinib. Recent Results Cancer Res. 2018;212:119-132. doi: 10.1007/978-3-319-91439-8_6. PMID: 30069628.
[3]. Quintás-Cardama A, Vaddi K, et,al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010 Apr 15;115(15):3109-17. doi: 10.1182/blood-2009-04-214957. Epub 2010 Feb 3. PMID: 20130243; PMCID: PMC3953826.
[4]. Hermans MAW, Schrijver B, et,al. The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release. Clin Exp Allergy. 2018 Nov;48(11):1412-1420. doi: 10.1111/cea.13217. Epub 2018 Aug 3. PMID: 29939445.
[5]. Xu N, Yang XF, et,al. Ruxolitinib reduces severe CRS response by suspending CAR-T cell function instead of damaging CAR-T cells. Biochem Biophys Res Commun. 2022 Mar 5;595:54-61. doi: 10.1016/j.bbrc.2022.01.070. Epub 2022 Jan 20. PMID: 35101664.
[6]. Bai Y, Wang W, et,al. Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice. Int J Biol Sci. 2020 Jan 1;16(2):194-203. doi: 10.7150/ijbs.39024. PMID: 31929748; PMCID: PMC6949153.
[7]. Hasan S, Hu L, et,al. Ruxolitinib ameliorates progressive anemia and improves survival during episodes of emergency granulopoiesis in Fanconi C-/- mice. Exp Hematol. 2022 May;109:55-67.e2. doi: 10.1016/j.exphem.2022.03.001. Epub 2022 Mar 9. PMID: 35278531; PMCID: PMC9064927.
Ruxolitinib (INCB18424)作为一种抑制剂，能够抑制Janus相关激酶(JAKs)JAK1和JAK2, IC50 分别为 3.3 nM 和 2.8 nM，Ruxolitinib介导对造血和免疫功能重要的若干细胞因子和生长因子信号[1-3]。
Ruxolitinib (INCB18424) (500nM-50μM;30min)显著抑制A23817和substance P诱导的HMC1细胞中IL-6、TNF-α和MCP-1的产生[4]。Ruxolitinib (0-400nM; 3days)降低CAR-T细胞中细胞因子的释放水平[5]。
Ruxolitinib (INCB18424)治疗(30 mg/kg; p.o.; twice a day 14 days)可减轻UUO小鼠肾损害[6]。Ruxolitinib治疗(twice daily by oral gavage; 2 weeks)改善JAK2V617F-driven的恶性疾病小鼠的生存能力和脾肿大情况[3]。用Ruxolitinib (45 mg/kg; i.p; 5 days/week)治疗Fancc-/-小鼠可减少贫血，增强粒细胞功能，延迟克隆进展，延长反复紧急粒细胞生成发作期间的生存期[7]。
|
Cell experiment [1]: |
|
|
Cell lines |
HMC1 cells |
|
Preparation method |
Cells were seeded in a 96-well plate at 2×105 cells in 200 μL culture medium per condition. Subsequently, the cells were incubated for 30 minutes with ruxolitinib before stimulating them with 1 μmol/L of A23187 or 5 μmol/L of substance P. TNF-α levels in the supernatant were measured after 6 hours of stimulation, and MCP-1 and IL-6 levels were measured after 24 hours of stimulation. |
|
Reaction Conditions |
500nM-50μM;30min |
|
Applications |
Ruxolitinib significantly inhibited the production of IL-6, TNF-α and MCP-1 as induced by A23817 and substance P in HMC1 cells. |
|
Animal experiment [2]: |
|
|
Animal models |
Male C57BL/6 mice |
|
Preparation method |
Mice were randomly assigned to three groups with 5 mice in each group as follows: (1) Sham-operated mice with vehicle (Sham); (2) Unilateral ureteral obstruction (UUO) mice with vehicle (UUO); (3) UUO mice treated with Ruxolitinib (UUO+RUX). To establish UUO model, mice were given general anesthesia by intraperitoneal injection of pentobarbital (50mg/kg body weight). The left ureter was exposed via a left flank incision, ligated with 4-0 silk at two points, and cut between the 2 ligation points. The Sham-operated group had no ligation. For in vivo experiments, Ruxolitinib was dissolved in PEG300/dextrose 5%l in a ratio of 1:3 (PEG/dex) and administered to mice by oral gavage at a dosage of 30 mg/kg twice daily for 14 days immediately after UUO or Sham-operation. The Sham and UUO group received PEG/dex alone as vehicle. Thel mice were sacrificed at days 14 after surgery. |
|
Dosage form |
30 mg/kg; p.o.; twice a day 14 days |
|
Applications |
Ruxolitinib treatment alleviated renal damage in UUO mice. |
|
References: [1]. Hermans MAW, Schrijver B, et,al. The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release. Clin Exp Allergy. 2018 Nov;48(11):1412-1420. doi: 10.1111/cea.13217. Epub 2018 Aug 3. PMID: 29939445. [2]. Bai Y, Wang W, et,al. Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice. Int J Biol Sci. 2020 Jan 1;16(2):194-203. doi: 10.7150/ijbs.39024. PMID: 31929748; PMCID: PMC6949153. |
|
| Cas No. | 941678-49-5 | SDF | |
| 别名 | 芦可替尼; INCB18424 | ||
| 化学名 | (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile | ||
| Canonical SMILES | C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3 | ||
| 分子式 | C17H18N6 | 分子量 | 306.37 |
| 溶解度 | ≥ 15.32mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.264 mL | 16.3201 mL | 32.6403 mL |
| 5 mM | 0.6528 mL | 3.264 mL | 6.5281 mL |
| 10 mM | 0.3264 mL | 1.632 mL | 3.264 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
-
Related Biological Data
Effects of ZSD on inflammatory signaling pathways. (C) and p–NF–kB, p-STAT3, and HIF-1α protein expression.
Then gavage ZSD-H (3.7 g/kg/day)), and ZSD-H + Ruxolitinib(Glpbio) group (rats were intranasal administration of LY294002 (2.2 mg/kg/day) 2 h before each OVA atomization inhalation.
J Ethnopharmacol 314 (2023): 116637 PMID: 37187363 IF: 5.3999 -
Related Biological Data
HSCB phosphorylation by phosphoinositol-3-kinase (PI3K) was necessary for its functionalization during erythropoiesis of K562 cells and CD34+CD90+ HSCs. (A) Western blotting analyses demonstrated that treatment with ruxolitinib and wortmannin, which are respectively inhibitors against Janus tyrosine kinase 2 (JAK2) and PI3K, increased the protein level of TACC3 and decreased FOG1 nuclear translocation.
After the FBS deprivation treatment, K562 cells were 468 incubated for 48 hours with 300 nM ruxolitinib (GlpBio).
bioRxiv (2024): 2024-02. PMID: 38757931