Ruxolitinib

别名: INCB018424 中文名称:鲁索替尼

Ruxolitinib是第一个应用于临床的,有效的,选择性JAK1/2抑制剂,在无细胞试验中IC50为3.3 nM/2.8 nM。作用于JAK1, JAK2与作用于JAK3相比,选择性高130多倍。Ruxolitinib 通过毒性线粒体自噬杀死肿瘤细胞。Ruxolitinib 可诱导自噬并增强细胞凋亡。

Ruxolitinib Chemical Structure

Ruxolitinib Chemical Structure

CAS: 941678-49-5

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 794.43 现货
5mg RMB 647.01 现货
25mg RMB 1941.03 现货
100mg RMB 4823.91 现货
1g RMB 12858.3 现货
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客户使用Selleck的Ruxolitinib发表文献551

产品质控

批次: 纯度: 99.98%
99.91

常与Ruxolitinib一起在实验中被使用的化合物

Linifanib (ABT-869)


Ruxolitinib和Linifanib联合对急性髓性白血病(AML)患者的FMS样酪氨酸激酶3 (FLT3)抑制具有协同作用。


Hart S, et al. Blood Cancer J. 2011 Nov;1(11):e44.

Ibrutinib


Ruxolitinib和Ibrutinib联合使用可有效抑制JAK信号,并在慢性淋巴细胞白血病(CLL)患者中具有良好的耐受性。


Spaner DE, et al. Cancer Med. 2019 Apr;8(4):1540-1550.

TP-3654


Ruxolitinib和TP-3654联合用药对MPLW515L小鼠骨髓(BM)纤维化的抑制作用显著增强。


Dutta A, et al. Leukemia. 2022 Mar;36(3):746-759.

Sonidegib


Ruxolitinib和Sonidegib联合使用可显著降低血细胞计数、突变等位基因负担和骨髓纤维化。


Kaplan JB, et al. EBioMedicine. 2016 Jan 13;3:17-25.

Hydroxyurea


Ruxolitinib和Hydroxyurea在减脾和提高OS方面具有显著优势,是一种有益的骨髓纤维化(MF)靶向治疗方法。


Li Y, et al. Ann Hematol. 2020 Jun;99(6):1161-1176.

Ruxolitinib相关产品

相关信号通路图

JAK抑制剂选择性比较

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
A549/DDP Function Assay 30 nM 48 h Down-regulation of STAT3 phosphorylation 25213670
NCI-H2347 Function Assay 30 nM 48 h Decrease in Bcl2 expression 25213670
NCI-H1299 Function Assay 30 nM 48 h Down-regulation of STAT3 phosphorylation 25213670
A549/DDP Apoptosis Assay 30 nM 48 h Induction of apoptosis 25213670
NCI-H1299 Apoptosis Assay 30 nM 48 h Induction of apoptosis 25213670
NCI-H2347 Apoptosis Assay 30 nM 48 h Induction of apoptosis 25213670
Hep3B Function Assay 1 μM 16 h Impaires the capacity of IHCA-associated gp130 mutants to active STAT3 with IC50 of ~50 μM 24501689
HepG2 Function Assay 1 μM 16 h Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3 24501689
Huh7 Function Assay 1 μM 16 h Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3 24501689
BaF3 Kinase Assay 80 nM 6 h Reduces the phosphorylation of STAT5 in JAK2V617F-mutated BAF3-EPOR cell 24237791
DLD-1 Kinase Assay 25 μM 48 h Inhibition of JAK1 phosphorylation 24050550
RKO Kinase Assay 25 μM 48 h Inhibition of JAK1 phosphorylation 24050550
DLD-1 Kinase Assay 25 μM 48 h Inhibition of JAK2 phosphorylation 24050550
RKO Kinase Assay 25 μM 48 h does not inhibit JAK1 phosphorylation 24050550
RKO Growth Inhibition Assay 50 μM 48 h IC50=14.76 μM 24050550
DLD-1 Growth Inhibition Assay 50 μM 48 h IC50=15.51 μM 24050550
DLD-1 Apoptosis Assay 25 μM 48 h Induces apoptosis by activating caspase 3 24050550
RKO Apoptosis Assay 25 μM 48 h Induces apoptosis by activating caspase 3 24050550
HuH7 Growth Inhibition Assay 50 μM 48 h >82% reduction 23941832
SNU182 Growth Inhibition Assay 50 μM 48 h >64% reduction 23941832
SNU423 Growth Inhibition Assay 50 μM 48 h >81% reduction 23941832
HuH7 Function Assay 50 μM 24 h Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
SNU182 Function Assay 50 μM 24 h Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
SNU423 Function Assay 50 μM 24 h Inhibition of STAT1 and STAT3 phosphorylation significantly 23941832
HT93A Growth Inhibition Assay 320 nM 5 d Inhibition of GCS-F induced granulocytic differentiation 25805962
SET-2 Cytotoxic Assay 5 μM 48 h Cytotoxic index=18.7% 25931349
HEL Cytotoxic Assay 5 μM 48 h Cytotoxic index=12.2% 25931349
TF1 Kinase Assay 20 min Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation with IC50 of 0.024μM 22698084
TF1 Kinase Assay 20 min Inhibition of JAK2 in human TF1 cells assessed as inhibition of EPO-induced STAT5 phosphorylation with IC50 of 0.012μM 22698084
Sf9 cells JAK inhibition assay 1 h Ki = 0.0001 μM 23668484
Sf9 cells JAK inhibition assay 1 h Ki = 0.0002 μM 23668484
Sf9 cells JAK inhibition assay 1 h Ki = 0.0005 μM 23668484
Sf21 cells JAK inhibition assay 1 h IC50 = 0.0028 μM 22591402
Sf21 cells JAK inhibition assay 60 min IC50 = 0.003 μM 27137359
Sf9 cells JAK inhibition assay 1 h Ki = 0.0032 μM 23668484
Sf21 cells JAK inhibition assay 1 h IC50 = 0.0033 μM 22591402
TF1 cells JAK inhibition assay 30 min IC50 = 0.00685 μM 23061660
TF1 cells JAK inhibition assay 20 min EC50 = 0.012 μM 22698084
Sf21 cells TYK2 inhibition assay 1 h IC50 = 0.019 μM 22591402
TF1 cells JAK inhibition assay 20 min EC50 = 0.024 μM 22698084
Sf21 cells JAK inhibition assay 1 h IC50 = 0.428 μM 22591402
CD34+ cells JAK inhibition assay 45 min IC50 = 0.677 μM 24417533
NCI-H2347 Growth Inhibition Assay IC50=0.17 μM 25213670
NCI-H1299 Growth Inhibition Assay IC50=0.28 μM 25213670
A549/DDP Growth Inhibition Assay IC50=0.22 μM 25213670
A549 Growth Inhibition Assay IC50=0.04 μM 25213670
NCI-H358 Growth Inhibition Assay IC50=0.1 μM 25213670
NCI-H460 Growth Inhibition Assay IC50=0.13 μM 25213670
CMK Growth Inhibition Assay Inhibition of CMK carrying the WT JAK cell proliferation with IC50 of 0.075 μM 25352124
CMK Growth Inhibition Assay Inhibition of CMK carrying the JAK3A63D mutation cell proliferation with IC50 of 0.163 μM 25352124
CMK Growth Inhibition Assay Inhibition of CMK carrying the JAK3A572V mutation cell proliferation 25352124
Human monocyte Kinase Assay Inhibition of JAK2/1 in human monocytes expressing CD14 assessed as inhibition of IFNgamma-stimulated STAT1 phosphorylation with IC50 of 0.031μM 23540648
Human monocyte Kinase Assay Inhibition of JAK2 in human monocytes expressing CD14 assessed as inhibition of GM-CSF-stimulated STAT5a phosphorylation with IC50 of 0.026μM 23540648
Human T cell Kinase Assay Inhibition of JAK3/1 in human T cells expressing CD3 assessed as inhibition of IL2-stimulated STAT5a phosphorylation with IC50 of 0.023μM 23540648
SET2 cells JAK inhibition assay IC50 = 0.00184 μM 23061660
CD34+ cells JAK inhibition assay IC50 = 0.008 μM 26927423
T cells JAK inhibition assay IC50 = 0.023 μM 23540648
T cells JAK inhibition assay IC50 = 0.023 μM 23540648
T cells JAK inhibition assay IC50 = 0.031 μM 23540648
T cells JAK inhibition assay IC50 = 0.031 μM 23540648
PBMC cells JAK inhibition assay IC50 = 0.04 μM 26927423
PBMC cells STAT5 inhibition assay IC50 = 0.448 μM 26927423
点击查看更多细胞系数据

生物活性

产品描述 Ruxolitinib是第一个应用于临床的,有效的,选择性JAK1/2抑制剂,在无细胞试验中IC50为3.3 nM/2.8 nM。作用于JAK1, JAK2与作用于JAK3相比,选择性高130多倍。Ruxolitinib 通过毒性线粒体自噬杀死肿瘤细胞。Ruxolitinib 可诱导自噬并增强细胞凋亡。
靶点
JAK2 [1]
(Cell-free assay)
JAK1 [1]
(Cell-free assay)
2.8 nM 3.3 nM
体外研究(In Vitro)
体外研究活性 在Ba/F3细胞和HEL细胞中,INCB018424有效地和有选择性地抑制JAK2V617F介导的信号传导和细胞增殖。INCB018424以剂量依赖性的方式显着地增加Ba/F3细胞的细胞凋亡。在Ba/F3细胞中,INCB018424(64 nM)致使线粒体去极化细胞增加一倍。INCB018424抑制来自正常捐助者和真性红细胞增多症患者的红细胞前体细胞的增殖,IC50分别是407 nM 和223 nM。 INCB018424有效抑制红细胞集落形成,IC50是67 nM。[1]
激酶实验 结合试验
重组蛋白是使用Sf21细胞和杆状病毒载体表达的,并通过亲和层析纯化。JAK激酶测定使用肽底物(-EQEDEPEGDYFEWLE)的均相时间分辨荧光测定法。酶反应是用Ruxolitinib或对照,JAK酶,500 nM肽,三磷酸腺苷(ATP; 1mM),和2%的二甲基亚砜(DMSO)反应1小时。 50%抑制浓度(IC50)时需要抑制50%荧光信号的INCB018424浓度。
细胞实验 细胞系 Ba/F3和HEL细胞
浓度 3 μM
孵育时间 48小时
方法 2×103细胞接种于的96孔板的一个孔中,用溶于DMSO的INCB018424(0.2%DMSO终浓度)在37℃和5% CO2条件下温育48小时。存活率是通过使用细胞滴度格洛荧光素酶试剂或活细胞计数器测定ATP水平。数值转换为相比对照的抑制百分率, IC50曲线使用Prism的GraphPad数据的非线性回归分析拟合。
实验图片 检测方法 检测指标 实验图片 PMID
Western blot cleaved PARP / cleaved caspase3 p-JAK2 / p-AKT / p-MAPK / Bcl-xl / MCL-1 c-Myc / c-Jun / Cyclin B / Cyclin D / Bcl-2 / HIF-1α p-STAT3 29849942
Growth inhibition assay Cell viability Cell apoptosis Cell proliferation 29849942
Immunofluorescence α-tubulin 26356819
体内研究(In Vivo)
体内研究活性 INCB018424(180 mg/kg,口服,每日两次)导致JAK2V617F驱动的小鼠模型的生存率在处理22天后大于90%。在JAK2V617F驱动的小鼠模型中,INCB018424(180 mg/kg,口服,每日两次)显着降低脾脏肿大和炎症因子的循环水平,并优先消灭肿瘤细胞,造成显著延长的生存期,无骨髓抑制或免疫抑制作用。[1] 在骨髓纤维化的双盲试验中,Ruxolitinib组的主要终点达到41.9%,安慰剂组则为0.7%。 Ruxolitinib导致脾体积持续减少和总症状得分提高50%或更多。[2] 在Ruxolitinib(15 mg,每天两次)组内,共28%骨髓纤维化患者至48周时脾脏体积减少至少35%,而接受最好的治疗组的比例为0%。Ruxolitinib致使脾脏长度减少了56%,而接受最好的治疗组却增加了4%。Ruxolitinib组患者的生活质量得到提高和骨髓纤维化相关症状减少。[3]
动物实验 Animal Models JAK2V617F驱动的小鼠模型
Dosages 180 mg/kg
Administration 口服
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05762640 Not yet recruiting
Haemophagocytic Lymphohistiocytosis
Assistance Publique - Hôpitaux de Paris
March 2024 Phase 2
NCT05998408 Not yet recruiting
Severe Aplastic Anemia|Single Lineage Cytopenias T-LGL|Hypoplastic MDS
National Heart Lung and Blood Institute (NHLBI)|National Institutes of Health Clinical Center (CC)
January 12 2024 Phase 1|Phase 2
NCT05998395 Recruiting
Kohlmeier Degos Disease With Neurologic Involvement
National Heart Lung and Blood Institute (NHLBI)|National Institutes of Health Clinical Center (CC)
September 28 2023 Phase 1|Phase 2

化学信息&溶解度

分子量 306.37 分子式

C17H18N6

CAS号 941678-49-5 SDF Download Ruxolitinib SDF
Smiles C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 61 mg/mL ( 199.1 mM; DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 12 mg/mL

Water : Insoluble

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

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)

mg/kg g μL

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Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

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,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法: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 ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意: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。

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常见问题及建议解决方法

问题 1:
What is the difference between S2902 and S1378 which seem to have same structure formula according to the product information?

回答:
These two chemicals are the two different chiral forms of Ruxolitinib. S2902 S-Ruxolitinib is the S form and S1378 Ruxolitinib is the D form. One of the carbon atoms in this molecule is asymmetric, making the two molecules mirror images of each other. The biological activities of these two molecules can be very different because of the confirmation differences.

问题 2:
How about the half-life of the compound (Ruxolitinib)? How long is the duration of the inhibitory effect on JAK-STAT signaling?

回答:
The half-life of this compound in body is about 2~3 hours according to previous study. Generally, it is longer in vitro culture medium than in vivo. In paper, Ruxolitinib was also used for 24hours. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=24711661.

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