AS1517499

Catalog No.S8685 Batch:S868502

Technical Data

Formula	C₂₀H₂₀ClN₅O₂
Molecular Weight	397.86	CAS No.	919486-40-1
Solubility (25°C)*	In vitro	DMSO	80 mg/mL (201.07 mM)
		Ethanol	20 mg/mL (50.26 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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

Targets

STAT6 ^[1]
(Cell-free assay)

21 nM

In vitro

AS1517499 inhibit IL-4-induced Th2 differentiation of mouse spleen T cells, but has no influence on Th1 differentiation induced by IL-12^[1]. AS1517499 is able to prevent the IL-4-activated STAT6-mediated increase of the clonogenic potential of primary PCa cells. At a dose of 300 nM, AS1517499 decreases the clonogenic potential of primary basal PCa cells^[3].

In vivo

In vivo treatment with AS1517499 ameliorates the antigen-induced bronchial smooth muscle (BSM) hyperresponsiveness by inhibiting the RhoA up-regulation in BSMs and, at least in part, by reducing the IL-13 production in the airways in mice^[2]. AS1517499 reduces preventive effects of apoptotic cell instillation on bleomycin-induced lung fibrosis by suppressing PPARγ^[4].

Protocol (from reference)

Cell Assay:^{^[2]}	Cell lines Normal human BSM cells Concentrations 100 nM Incubation Time 30 min Method Cells are maintained in SmBM medium supplemented with 5% fetal bovine serum, 0.5 ng/ml human epidermal growth factor (hEGF), 5 mg/ml insulin, 2 ng/ml human fibroblast growth factor-basic (hFGF-b), 50 mg/ml gentamicin, and 50 ng/ml amphotericin B. Cells are maintained at 37℃ 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 is observed, cells are cultured without serum for 24 hours before addition of recombinant human IL-13. AS1517499, 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 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.
Animal Study:^{^[2]}	Animal Models A murine model of allergic bronchial asthma (Male BALB/c mice) Dosages 1 or 10 mg/kg/d Administration i.p.

Cell Assay:^{^[2]}

Cell lines
Normal human BSM cells
Concentrations
100 nM
Incubation Time
30 min
Method
Cells are maintained in SmBM medium supplemented with 5% fetal bovine serum, 0.5 ng/ml human epidermal growth factor (hEGF), 5 mg/ml insulin, 2 ng/ml human fibroblast growth factor-basic (hFGF-b), 50 mg/ml gentamicin, and 50 ng/ml amphotericin B. Cells are maintained at 37℃ 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 is observed, cells are cultured without serum for 24 hours before addition of recombinant human IL-13. AS1517499, 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 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.

Animal Study:^{^[2]}

Animal Models
A murine model of allergic bronchial asthma (Male BALB/c mice)
Dosages
1 or 10 mg/kg/d
Administration
i.p.

References

[4] Kim MJ, et al. Cell Physiol Biochem. 2018, 45(5):1863-1877.

+ Expand

Selleck's AS1517499 has been cited by 19 publications

Transcriptional and chromatin profiling of human blood innate lymphoid cell subsets sheds light on HIV-1 pathogenesis [ EMBO J, 2023, e114153.]	PubMed: 37382276
JAK-STAT signalling shapes the NF-κB response in CLL towards venetoclax sensitivity or resistance via Bcl-XL [ Mol Oncol, 2023, 17(6):1112-1128]	PubMed: 36550750
Co-induced Allergic Response to an Unrelated Allergen Exacerbates Imiquimod-Induced Psoriasis in Mice [ Biol Pharm Bull, 2023, 46(10):1484-1489]	PubMed: 37599076
A novel targeted iron oxide nanocarrier for inhibiting M2-type macrophages in the tumor microenvironment [ Journal of Cancer Research and Therapeutics, 2022-, 18(5):p 1409-1416]	PubMed: None
Ketone body β-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway [ BMC Med, 2022, 20(1):148]	PubMed: 35422042
STAT6 contributes to renal fibrosis by modulating PPARα-mediated tubular fatty acid oxidation [ Cell Death Dis, 2022, 13(1):66]	PubMed: 35046382
Soluble SIRP-Alpha Promotes Murine Acute Lung Injury Through Suppressing Macrophage Phagocytosis [ Front Immunol, 2022, 13:865579]	PubMed: 35634325
Therapeutic Targeting of Cancer Stem Cells Prevents Resistance of Colorectal Cancer Cells to MEK Inhibition [ ACS Pharmacol Transl Sci, 2022, 5(9):724-734]	PubMed: 36110381
Dabigatran activates inflammation resolution by promoting fibrinogen-like protein 2 shedding and RvD5n-3 DPA production [ Theranostics, 2021, 11(9):4251-4261]	PubMed: 33754059
Tumor-derived microparticles promote the progression of triple-negative breast cancer via PD-L1-associated immune suppression [ Cancer Lett, 2021, 523:43-56]	PubMed: 34601021

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.