您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > JAK3-IN-6
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
JAK3-IN-6
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
JAK3-IN-6图片
CAS NO:1443235-95-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)350.38
FormulaC19H18N4O3
CAS No.1443235-95-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM
Water: N/A
Ethanol: N/A
Chemical NameEthyl 4-(3-methacrylamidophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate
SynonymsJAK3-IN-2; JAK3IN2; JAK3 IN 2; JAK3IN-2; JAK3-IN2
SMILES CodeO=C(C1=CNC2=NC=NC(C3=CC=CC(NC(C(C)=C)=O)=C3)=C21)OCC
实验参考方法

Reversible janus associated kinase (JAK) inhibitors such as tofacitinib and decernotinib block cytokine signaling and are efficacious in treating autoimmune diseases. However, therapeutic doses are limited due to inhibition of other JAK/signal transducer and activator of transcription pathways associated with hematopoiesis, lipid biogenesis, infection, and immune responses. A selective JAK3 inhibitor may have a better therapeutic index; however, until recently, no compounds have been described that maintain JAK3 selectivity in cells, as well as against the kinome, with good physicochemical properties to test the JAK3 hypothesis in vivo. To quantify the biochemical basis for JAK isozyme selectivity, we determined that the apparent Km value for each JAK isozyme ranged from 31.8 to 2.9 μM for JAK1 and JAK3, respectively. To confirm compound activity in cells, we developed a novel enzyme complementation assay that read activity of single JAK isozymes in a cellular context. Reversible JAK3 inhibitors cannot achieve sufficient selectivity against other isozymes in the cellular context due to inherent differences in enzyme ATP Km values. Therefore, we developed irreversible JAK3 compounds that are potent and highly selective in vitro in cells and against the kinome. Compound 2, a potent inhibitor of JAK3 (0.15 nM) was 4300-fold selective for JAK3 over JAK1 in enzyme assays, 67-fold [interleukin (IL)-2 versus IL-6] or 140-fold [IL-2 versus erythropoietin or granulocyte-macrophage colony-stimulating factor (GMCSF)] selective in cellular reporter assays and>35-fold selective in human peripheral blood mononuclear cell assays (IL-7 versus IL-6 or GMCSF). In vivo, selective JAK3 inhibition was sufficient to block the development of inflammation in a rat model of rheumatoid arthritis, while sparing hematopoiesis.

References: J Pharmacol Exp Ther. 2017 May;361(2):229-244.