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AS1517499

Katalog-Nr.GC19039

AS1517499 ist ein potenter und gehirndurchlÄssiger STAT6-Phosphorylierungsinhibitor mit einem IC50 von 21 nM.

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AS1517499 Chemische Struktur

Cas No.: 919486-40-1

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10mM (in 1mL DMSO)
76,00 $
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1mg
30,00 $
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2mg
42,00 $
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5mg
73,00 $
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10mg
112,00 $
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25mg
173,00 $
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50mg
258,00 $
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100mg
379,00 $
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500mg
817,00 $
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

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[2].

Animal experiment:

Mice[2] Male BALB/c mice are used. Preparation of a murine model of allergic bronchial asthma, which has an in vivo AHR, is performed. In brief, BALB/c mice (8 wk of age) are actively sensitized by intraperitoneal injections of 8 μg ovalbumin (OVA) with 2 mg Imject Alum on Day 0 and Day 5. The sensitized mice are challenged with aerosolized OVA-saline solution (5 mg/mL) for 30 minutes on Days 12, 16, and 20. A control group of mice received the same immunization procedure but inhaled saline aerosol instead of OVA challenge. The aerosol is generated with an ultrasonic nebulizer and introduced to a Plexiglas chamber box (130×200 mm, 100 mm height) in which the mice are placed. Animals also received intraperitoneal injection with AS1517499 (1 or 10 mg/kg/d; dissolved in 20% DMSO in saline) or its vehicle 1 hour before each antigen inhalation (Days 12, 16, and 20). Twenty-four hours after the last OVA challenge, mice are killed by exsanguination from abdominal aorta under urethane (1.6 g/kg, intraperitoneally) anesthesia.

References:

[1]. Nagashima S, et al. Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors. Bioorg Med Chem. 2007 Jan 15;15(2):1044-55.
[2]. Chiba Y, et al. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24.

Background

AS1517499 is a potent STAT6 inhibitor with an IC50 of 21 nM.

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[1]. 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)[2].

In 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. These mice have an augmented BSM contractility to acetylcholine together with an up-regulation of RhoA in bronchial tissues. Intraperitoneal injections of AS1517499 (10 mg/kg) 1 hour before each ovalbumin exposure inhibits both the antigen-induced up-regulation of RhoA and BSM hyperresponsiveness, almost completely[2].

References:
[1]. Nagashima S, et al. Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors. Bioorg Med Chem. 2007 Jan 15;15(2):1044-55.
[2]. Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24.

Chemical Properties

Cas No. 919486-40-1 SDF
Canonical SMILES O=C(C1=CN=C(NCCC2=CC=C(O)C(Cl)=C2)N=C1NCC3=CC=CC=C3)N
Formula C20H20ClN5O2 M.Wt 397.86
Löslichkeit DMSO : ≥ 35 mg/mL (87.97 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.5134 mL 12.5672 mL 25.1345 mL
5 mM 0.5027 mL 2.5134 mL 5.0269 mL
10 mM 0.2513 mL 1.2567 mL 2.5134 mL
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