S-Ruxolitinib 鲁索利尼

目录号 M3030 所有产品仅供科研使用，严禁用于人或动物的治疗等任何其他用途，不为任何个人提供产品和服务

S-Ruxolitinib (INCB018424)是第一个有效的，选择性JAK1/2抑制剂，IC50为3.3 nM/2.8 nM，作用于JAK1/2比作用于JAK3选择性高130倍以上。

别名：S-Ruxolitinib; INCB18424

其他规格数量报价？

INCB018424作用于Ba/F3细胞和HEL细胞，有效且选择性抑制JAK2V617F介导的信号和增殖。INCB018424作用于Ba/F3细胞，显著增强凋亡，这种作用具有剂量依赖性。INCB018424(64 nM) 作用于Ba/F3细胞，导致细胞线粒体去极化增加一倍。

Blood Cancer J. 2016 Oct 7;6(10):e481.

Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.
Nature. 2014 Aug 7;512(7512):78-81.

Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms.

	数据来源	Blood cancer journal (2016) . Figure 4. ruxolitinib (Abmole Bioscience, Houston, TX, USA) and fedratinib (Abmole Bioscience)
	方法	Western blotting
	细胞系/动物模型	Embroys of wild-type zebrafish
	浓度	1 μM ~ 8 μM
	处理时间	24 h
	实验结果	The expression of CALRdel52 mRNA significantly increased stat5 phosphorylation (Figure 4a, lane 2). Furthermore, treatment with ruxolitinib and fedratinib significantly ameliorated the enhanced stat5 phosphorylation induced by CALR-del52 mRNA (Figure 4a, lane 3 and 4). In addition, treatment with ruxolitinib significantly decreased the numbers of CD41+ thrombocytes in uninjected control as well as CALR-del52-injected embryos in a dose-dependent manner (Figure 4b). Whereas treatment with fedratinib only had minimal inhibitory effect on the number of CD41+ thrombocytes in uninjected control embryos, and had a modest and significant dose-independent inhibitory effect on mutant CALR-induced thrombocytosis (Figure 4c). Our results demonstrated that mutant CALR-mediated pathogenic thrombopoiesis involves jak-stat activation that can be blocked by JAK inhibitors.

	数据来源	Nature (2014). Figure 1. The JAK inhibitor INCB018424 (S-ruxolitinib, Abmole Bioscience)
	方法	automated blood counter, flowcytometry
	细胞系/动物模型	haematopoietic cell and BM MSCs
	浓度	oral gavage (30mg/kg, twice per day separated 10–12h)
	处理时间	4 weeks
	实验结果	Nestin1 MSC reduction was instead explained by a threefold increased apoptotic rate in mutant mice, and was not prevented by the JAK inhibitor ruxolitinib. Treatment with the JAK1/2 inhibitor ruxolitinib reduces haematopoietic cell expansion in MPN but it does not rescue BM MSCs.

体外实验*
细胞系	Ba/F3-EpoR-JAK2V617F or HEL cells
方法	Cells were seeded at 2000/well of white bottom 96-well plates, treated with compounds from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37°C with 5% CO2. Viability was measured by cellular ATP determination using the Cell-Titer Glo (Promega) luciferase reagent or viable cell counting. Values were transformed to percent inhibition relative to vehicle control, and IC50 curves were fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
浓度	0~10µM
处理时间	48h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	6- to 8-week-old female BALB/c mice Ba/F3-JAK2V617F cells model
配制	5% dimethyl acetamide, 0.5% methocellulose
剂量	180mg/kg, twice a day
给药处理	orally

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	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

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的K_m系数
	动物 A的K_m系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

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