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Decernotinib

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Chemical Structure| 944842-54-0 同义名 : VX-509;VRT-831509;Adelatinib.;VRT 831509 . PubChem CID 59422203. Decernotinib
CAS号 : 944842-54-0
货号 : A306535
分子式 : C18H19F3N6O
纯度 : 99%+
分子量 : 392.378
MDL号 : MFCD27987896
存储条件：

粉末 Keep in dark place,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: 50 mg/mL(127.43 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 3.5 mg/mL clear

PO 0.5% CMC-Na 42 mg/mL suspension

生物活性
靶点

  • JAK1

    JAK1, IC50:11 nM

    JAK1, Ki:11 nM

  • JAK3

    JAK3, Ki:2.5 nM

  • Tyk2

    TYK2, Ki:13 nM

  • JAK2

    JAK2, Ki:13 nM
描述 Janus kinases (JAKs) includes cytokines, growth factors, and other chemical messengers rely on a class of intracellular nonreceptor tyrosine kinases can rapidly transduce intracellular signals. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. JAK3 is of particular interest due to its importance in immune function and its expression, which is largely confined to lymphocytes, thus limiting the potential impact of JAK3 inhibition on nonimmune physiology. JAK-STAT dysregulation results in autoimmune disorders such as rheumatoid arthritis, ulcerative colitis, and Crohn disease[3]. Decernotinib （VX-509） potently inhibits JAK3 in enzyme assays with Ki of 2.5 nM and cellular assays dependent on JAK3 activity with IC50 ranging from 50-170 nM. JAK3 inhibition by VX-509 was determined with an (interleukin) IL-2-induced STAT-5 phosphorylation assay in an IL-2-dependent T-cell line (HT-2). In the IL-2-stimulated HT-2-phosphorylated STAT-5 fluorescence-activated cell sorting assay, VX-509 had an IC50 of 99 ± 40 nM. VX-509 showed statistically significant, dose-dependent inhibition of the increases in ankle diameter and paw weight that occur in response to collagen injections in rats treated with VX-509 b.i.d. at doses of 10, 25, or 50 mg/kg or etanercept at 10 mg/kg. Inhibition of ankle diameter increase was significant with VX-509 at 10 mg/kg b.i.d. (55% inhibition), 25 mg/kg b.i.d. (70% inhibition), 50 mg/kg b.i.d. (76% inhibition), or 10 mg/kg etancercept (55% inhibition) relative to collagen plus vehicle-treated rats[4].
作用机制 Decernotinib can bind to ATP binding pockets of JAK2 with hinge hydrogen bonds to Leu 932.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.55mL

0.51mL

0.25mL

12.74mL

2.55mL

1.27mL

25.49mL

5.10mL

2.55mL
参考文献

[1]Mahajan S, Hogan JK, et al. VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease. J Pharmacol Exp Ther. 2015 May;353(2):405-14.

[2]Farmer LJ, Ledeboer MW, et al. Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases. J Med Chem. 2015 Sep 24;58(18):7195-216.

[3]Roskoski R Jr. Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol Res. 2016 Sep;111:784-803. doi: 10.1016/j.phrs.2016.07.038. Epub 2016 Jul 26. PMID: 27473820.

[4]Mahajan S, Hogan JK, Shlyakhter D, Oh L, Salituro FG, Farmer L, Hoock TC. VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease. J Pharmacol Exp Ther. 2015 May;353(2):405-14. doi: 10.1124/jpet.114.221176. Epub 2015 Mar 11. PMID: 25762693.