AS1517499

Catalog No.S8685 Batch:S868503

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.)

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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 26 publications

Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling [ Nature, 2024, 625(7996):778-787]	PubMed: 38081297
Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis [ Bone Res, 2024, 12(1):15]	PubMed: 38433252
Nicotinamide phosphoribosyltransferase prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice [ Theranostics, 2024, 14(7):2794-2815]	PubMed: 38773984
Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin [ Cell Rep, 2024, 43(7):114364]	PubMed: 38900635
Suppressive Activity of Boiogito, a Japanese Traditional Kampo Medicine, on Periostin Secretion in Human Fibroblast-Like Synoviocytes In Vitro [ Cureus, 2024, 16(4):e57690]	PubMed: 38711706
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
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
Electroacupuncture Alleviates Neuroinflammation by Regulating Microglia Polarization via STAT6/PPARγ in Ischemic Stroke Rats [ Neuroscience, 2023, 532:23-36]	PubMed: 37741355
Co-induced Allergic Response to an Unrelated Allergen Exacerbates Imiquimod-Induced Psoriasis in Mice [ Biol Pharm Bull, 2023, 46(10):1484-1489]	PubMed: 37599076

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