AS1517499 |
| カタログ番号GC19039 |
AS1517499 は、強力で脳透過性の STAT6 リン酸化阻害剤であり、IC50 は 21 nM です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 919486-40-1
Sample solution is provided at 25 µL, 10mM.
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AS1517499 is a potent and brain-permeable STAT6 inhibitor with IC50 of 21 nM. AS1517499 often plays a role in the treatment of renal fibrosis and Keloids[1-2].
AS1517499 inhibited the proliferation of keloid fibroblasts (KFs) and normal skin tissue fibroblasts (NFs) with IC50 values of 1055-1958 nM and 3688-4130 nM, respectively, and AS1517499 significantly downregulated the expression of p-STAT6 in KF at 400 and 800 nM[2]. AS1517499 significantly downregulated the transcriptional levels of M2 macrophage-related genes (t IL−10 = 5.403, t TGF−β = 7.213, t CD206 = 48.940, t Arg1 = 11.253), and could also completely inhibit and block the STAT6/PPARγ pathway and the activation of macrophage M2 polarization[3].
AS1517499 (10 mg/kg ) can effectively reduce the levels of Th2-related cytokines in atopic dermatitis(AD) mice, alleviate airway eosinophil and lymphocyte infiltration, and regulate GATA3/Foxp3 levels and subepithelial collagen deposition[4]. AS1517499 (10 mg/kg) effectively inhibited the activation of STAT6 observed in mouse peritoneal macrophages and spleen after injection of zymosan. Furthermore, AS1517499 reduced the zymosan-mediated increase in IL-10, TGFβ, and HGF in peritoneal lavage fluid (PLF)[5].
References:
[1] Jiao B, An C, Tran M, et al. Pharmacological inhibition of STAT6 ameliorates myeloid fibroblast activation and alternative macrophage polarization in renal fibrosis[J]. Frontiers in immunology, 2021, 12: 735014.
[2] Chao H, Zheng L, Hsu P, He J, Wu R, Xu S, Zeng R, Zhou Y, Ma H, Liu H, Tang Q. IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation. JCI Insight. 2023 Mar 22;8(6):e157091.
[3] Yan S W, Zhang R, Guo X, et al. Trichinella spiralis dipeptidyl peptidase 1 suppressed macrophage cytotoxicity by promoting M2 polarization via the STAT6/PPARγ pathway[J]. Veterinary Research, 2023, 54(1): 77.
[4] Li X, Han Z, Wang F, et al. The STAT6 inhibitor AS1517499 reduces the risk of asthma in mice with 2, 4-dinitrochlorobenzene-induced atopic dermatitis by blocking the STAT6 signaling pathway[J]. Allergy, Asthma & Clinical Immunology, 2022, 18(1): 12.
[5] Lee, Y.-J.; Kim, K.; Kim, M.; Ahn, Y.-H.; Kang, J.L. Inhibition of STAT6 Activation by AS1517499 Inhibits Expression and Activity of PPARγ in Macrophages to Resolve Acute Inflammation in Mice. Biomolecules 2022, 12, 447.
| Cell experiment [1]: | |
Cell lines | Keloid fibroblasts (KFs) and normal skin tissue fibroblasts (NFs) |
Preparation Method | Primary fibroblasts were treated with AS1517499 at concentrations ranging from 3.387 nM to 200 μM for 3 days, and the sensitivity of primary fibroblasts to AS1517499 was analyzed using the CCK-8 assay. |
Reaction Conditions | 3.387 nM to 200 μM, 3 days |
Applications | AS1517499 inhibits the proliferation of primary fibroblasts KFs and NFs with IC50 values of 1055-1958 nM and 3688-4130 nM, respectively. |
| Animal experiment [2]: | |
Animal models | Intracardiac Brain Metastasis Model |
Preparation Method | One week after intracardiac injection of 4T1-GFP cells, mice were subcutaneously implanted with osmotic minipumps. After 48 hours of in vivo priming, mice were treated with AS1517499 (11.43 mg/mL;10.6 mg/kg/week) or vehicle (50% DMSO in water) for 7 days. |
Dosage form | 10.6 mg/kg/week, 7days, s.c. |
Applications | AS1517499 treatment suppressed the anti-inflammatory phenotype of BDM/microglia, and reduced Arg1 expression in TMEM119+F4/80+ microglia. |
References: | |
| 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 |
| 溶解度 | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| 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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)
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