AS1517499
目录号 : GC19039
AS1517499 是一种有效的、可透过血脑屏障的 STAT6 抑制剂，IC50 为 21 nM。AS1517499常在肾纤维化及瘢痕的治疗中发挥作用。
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 | ||
| 分子式 | C20H20ClN5O2 | 分子量 | 397.86 |
| 溶解度 | DMSO : ≥ 35 mg/mL (87.97 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet