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Ruxolitinib

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Chemical Structure| 941678-49-5 同义名 : 鲁索替尼 ;INCB18424;INCB 018424
CAS号 : 941678-49-5
货号 : A272323
分子式 : C17H18N6
纯度 : 98%
分子量 : 306.365
MDL号 : MFCD12031592
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(342.73 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+water 5 mg/mL

生物活性
靶点

  • JAK1

    JAK1, IC50:3.3 nM

  • JAK2

    JAK2, IC50:2.8 nM
描述 JAK2 (Janus kinase 2) is a non-receptor tyrosine kinase. The mutation of it, JAK2V617F, which activates JAK2 signaling, is discovered in patients with myeloproliferative neoplasms[2]. Ruxolitinib, also called as INCB018424, is the first potent, selective, oral JAK1/JAK2 inhibitor to enter the clinic with IC50 values of 3.3 nM and 2.8 nM (measured by homogeneous time-resolved fluorescence assay), respectively. A dose-dependent reduction in the phosphorylated forms of JAK2, STAT5 and ERK1/2 can be seen in Ba/F3-EpoRJAK2V617F cells treated with ruxolitinib, which has constitutive phosphorylation of JAK2 as well as downstream targets. Ruxolitinib inhibits hematopoietic progenitor cell proliferation in primary MPN patient samples. Orally treatment of ruxolitinib can improve viability and splenomegaly in a JAK2V617F-driven mouse model of malignant disease[1]. Ruxolitinib is mainly used in treatment of myelofibrosis and autoimmune diseases due its anti-inflammatory and immunomodulating activity, such as affecting DC differentiation and function of leading to impaired T-cell activation significantly[3].
作用机制 Ruxolitinib binds in the ATP binding pocket of the kinase domain in its active configuration.[4]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A549 Growth Inhibition Assay IC50=0.04 μM 25213670
A549/DDP Growth Inhibition Assay IC50=0.22 μM 25213670
A549/DDP 30 nM Function Assay 48 h Down-regulation of STAT3 phosphorylation 25213670
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03274778 Prostate Cancer Not Applicable Recruiting May 1, 2019 Switzerland ... 展开 >> Istituto Oncologico della Svizzera Italiana (IOSI) Recruiting Bellinzona, Switzerland, 6500 Contact: Ricardo Pereira Mestre, Dr. med.    +41 (0)91 811 84 46    Ricardo.PereiraMestre@eoc.ch    Contact: Barbara Marongiu    +41 (0)91 811 91 20    barbara.marongiu@eoc.ch 收起 <<
NCT02120417 - Terminated(The study was termi... 展开 >>nated as other related studies of ruxolitinib did not provide sufficient efficacy to warrant continuation.) 收起 << - -
NCT01914484 Chronic Phase Chronic Myeloid ... 展开 >>Leukemia Accelerated Phase Chronic Myeloid Leukemia Blastic Phase Chronic Myeloid Leukemia Philadelphia Positive Acute Lymphoblastic Leukemia Resistant to Tyrosine Kinase Inhibitor Therapy 收起 << Phase 1 Phase 2 Unknown July 2016 Canada, Ontario ... 展开 >> Princess Margaret Hospital / University Health Network Recruiting Toronto, Ontario, Canada, M5G 2M9 Contact: Sima Bogomilsky, RN BScN CON(C)    416-946-4646    sima.bogomilsky@uhn.on.ca    Contact: Sonal Malhotra, M.Sc., Ph.D,CCRP    416-946-4501 ext 3449    sonal.malhotra@uhn.ca    Principal Investigator: Dennis Kim, MD/PhD          Sub-Investigator: Jeffrey H Lipton, MD/PhD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.26mL

0.65mL

0.33mL

16.32mL

3.26mL

1.63mL

32.64mL

6.53mL

3.26mL
参考文献

[1]Quint¨¢s-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.

[2]Hobbs GS, Rozelle S, et al. The Development and Use of Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms. Hematol Oncol Clin North Am. 2017 Aug;31(4):613-626.

[3]Heine A, Held SA, et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood. 2013 Aug 15;122(7):1192-202.

[4]Silvennoinen O, Hubbard SR, et al. Targeting the Inactive Conformation of JAK2 in Hematological Malignancies. Cancer Cell. 2015 Jul 13;28(1):1-2