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Ruxolitinib (INCB018424)

现货
Catalog No.
A3012
JAK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 700.00
现货
5mg
¥ 700.00
现货
25mg
¥ 1,500.00
现货
100mg
¥ 2,800.00
现货

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Background

Ruxolitinib dihydrochloride is a specific inhibitor of Janus-associated kinase (JAK1 and JAK2). Ruxolitinib is a small molecular with the formula of C17H21N6O4Pand Molecular Weight of 404. Ruxolitinib phosphate is an administered ATP-competitive cyclopentylpropionitrile derivative and shows inhibition activity on JAK1 and JAK2. Ruxolitinib inhibits phosphorylation of JAK1/2, STAT5, and ERK1/2, resulting in reduced cellular proliferation.

References

1. Ruxolitinib inhibits transforming JAK2 fusion proteins in vitro and induces complete cytogenetic remission in t (8; 9)(p22; p24)/PCM1-JAK2–positive chronic. E Lierman, D Selleslag, S Smits, J Billiet. Blood. 2012

2. Ruxolitinib for the treatment of myelofibrosis. A Ostojic, R Vrhovac, S Verstovsek.  Ther Clin Risk Manag. 2011

文献引用

1. Hermans MAW, Schrijver B, et al. "The JAK1/JAK2- inhibitor ruxolitinib inhibits mast cell degranulation and cytokine release." Clin Exp Allergy. 2018 Jun 25. PMID:29939445
2. Zhang S, Li Z, et al. "Interleukin-4 Enhances the Sensitivity of Human Monocytes to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Through Upregulation of Death Receptor 4." J Interferon Cytokine Res. 2018 Apr;38(4):186-194. PMID:29638207
3. Hall BM, Balan V, et al. "p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli." Aging (Albany NY). 2017 Aug 2;9(8):1867-1884. PMID:28768895
4. Radhakrishnan H, Ilm K, et al. "MACC1 regulates Fas mediated apoptosis through STAT1/3 - Mcl-1 signaling in solid cancers." Cancer Lett. 2017 Jun 23. pii: S0304-3835(17)30402-0. PMID:28649004

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt306.37
Cas No.941678-49-5
FormulaC17H18N6
SynonymsRuxolitinib,INCB018424,INCB-018424
Solubility≥15.32mg/mL in DMSO
Chemical Name(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
SDFDownload SDF
Canonical SMILESC1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

PV患者或正常对照者体内分离的原代单核细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

IC50:红系祖细胞:正常捐献者 407 nM,PV捐献者 223 nM。 髓系祖细胞:正常捐献者 511 nM,PV捐献者 444 nM。时间:14天

应用

在逐渐增加浓度的INCB018424存在时,红系(BFU-E)和骨髓来源(CFU-M)克隆祖细胞的生长用集落形成实验进行评估。INCB018424剂量依赖地抑制红系和髓系祖细胞的生长,其对正常捐献者和PV患者来源的红系祖细胞的平均IC50值分别为407 nM和223 nM。而对对照和PV样品来源的髓系祖细胞(CFU-M)的IC50值分别为511 nM和444 nM。

动物实验[2]:

动物模型

C57BL/6N小鼠

剂量

75 mg/kg;口服给药

应用

小鼠在注射OVA/CpG之前或之后6 h口服给药75 mg/kg的ruxolitinib或对照,并分析CD11c 1CD81脾DCs活化标志物的表达水平。在ruxolitinib治疗小鼠中,CD40、CD80、CD86以及MHC I和II分子的表达水平均降低。小鼠在注射OVA/CpG和转入CFSE标记的OT-I细胞之前6小时或之后6小时和18小时口服给药ruxolitinib或对照,在ruxolitinib预处理小鼠中,对转入的CFSE标记OT-I细胞的分析表明,ruxolitinib减少细胞增殖、CD25的表达以及IFN的产生。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Quintás-Cardama A, Vaddi K, Liu P, 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] Heine A, Held S A E, Daecke S N, et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood, 2013, 122(7): 1192-1202.

生物活性

描述 Ruxolitinib (INCB018424)是第一个用于临床的、有效的和选择性的JAK1/2抑制剂,IC50值为3.3 nM/2.8 nM,比对JAK3的选择性高130多倍。
靶点 JAK1 JAK2        
IC50 3.3 nM 2.8 nM        

质量控制

化学结构

Ruxolitinib (INCB018424)

相关生物数据

INCB018424
106 BaF3 Aut (V658I), Aut (F958V) were treated for 30 min with 100 nM, 1 μM or 10 μM INCB018424 inhibitor or with DMSO as a control (-condition), lysed and subjected to Western blot analysis. Phosphorylation of JAK1 and STAT5 was detected using specific anti-pY1034/35 JAK1 and anti-pY694 STAT5. Membranes were re-probed with anti-JAK1, anti-STAT5 and anti-β-Actin antibodies as a control. Similar results were obtained in 3 independent experiments.

相关生物数据

Ruxolitinib (INCB018424)

相关生物数据

Ruxolitinib (INCB018424)

相关生物数据

Ruxolitinib (INCB018424)

相关生物数据

Ruxolitinib (INCB018424)