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AS1517499
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。
AS1517499图片
CAS NO:919486-40-1
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

产品介绍
理化性质和储存条件
Molecular Weight (MW) 397.86
Formula C20H20ClN5O2
CAS No. 1448428-04-3 (free base); 919486-40-1; 1448428-05-4 (HCl);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 35 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES CodeO=C(C1=CN=C(NCCC2=CC=C(O)C(Cl)=C2)N=C1NCC3=CC=CC=C3)N
Synonyms

AS-1517499; AS1517499; AS 1517499

Chemical Name: 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide

Exact Mass: 445.20264

实验参考方法
In Vitro

In vitro activity: AS1517499 shows potent STAT6 inhibition with an IC50 value of 21 nM, and also inhibits IL-4-induced Th2 differentiation of mouse spleen T cells with an IC50 value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12.


Kinase Assay: AS1517499 shows potent STAT6 inhibition with an IC50 value of 21 nM, and also inhibits IL-4-induced Th2 differentiation of mouse spleen T cells with an IC50 value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12. AS1517499 selectively inhibits Th2 differentiation without affecting Th1 differentiation. In cultured human BSM cells, IL-13 (100 ng/mL) causes a phosphorylation of STAT6 and an up-regulation of RhoA, a monomeric GTPase responsible for Ca2+ sensitization of smooth muscle contraction: both events are inhibited by co-incubation with AS1517499 (100 nM).


Cell Assay: Normal human BSM cells (hBSMCs) are maintained in SmBM medium supplemented with 5% fetal bovine serum, 0.5 ng/mL human epidermal growth factor (hEGF), 5 μg/mL insulin, 2 ng/mL human fibroblast growth factor-basic (hFGF-b), 50 μg/mL gentamicin, and 50 ng/mL amphotericin B. Cells are maintained at 37°C in a humidified atmosphere (5% CO2), fed every 48 to 72 hours, and passaged when cells reached 90 to 95% confluence. Then the hBSMCs (passages 7-9) are seeded in 6-well plates and 8-well chamber slides at a density of 3,500 cells/cm2 and, when 80 to 85% confluence observed, cells are cultured without serum for 24 hours before addition of recombin is ant human IL-13. AS1517499 (100 nM) or its vehicle (0.3% DMSO) is treated 30 minutes before the addition of IL-13 (100 ng/mL). In some experiments, AS1517499 is treated 0 (co-incubation), 3, or 12 hours after the addition of IL-13. In another series of experiments, a selective Rho-kinase inhibitor Y-27632 (1 μM) or its vehicle (0.3% DMSO) is also applied 15 minutes before the IL-13 application. At the indicated time after the IL-13 treatment, cells are washed with PBS, immediately collected, and disrupted with 1× SDS sample buffer (250 μL/well), and used for Western blot analyses.

In VivoIn BALB/c mice that are actively sensitized and repeatedly challenged with ovalbumin antigen, an increased IL-13 level in bronchoalveolar lavage fluids and a phosphorylation of STAT6 in bronchial tissues are observed after the last antigen challenge.
Animal modelMale BALB/c mice
Formulation & Dosage 1 or 10 mg/kg/d; dissolved in 20% DMSO in saline or its vehicle; i.p injection
References Bioorg Med Chem. 2007 Jan 15;15(2):1044-55; Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24.