SAR-20347
目录号 : GC19320
A JAK family kinase inhibitor
Cas No.:1450881-55-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | Kinases are prepared in Base Reaction Buffer (20 mM Hepes pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO) and substrate is added with 1.5 mM CaCl2, 16 μg/mL Calmodulin, and 2 mM MnCl2. Varying concentrations of SAR-20347 in DMSO are added to the kinase reaction along with 10 μM 33P-ATP (activity 0.01 μCi/μL final) for IC50 determination[1]. |
Cell experiment: | Cells are plated in a 96-well v-bottom plate in starvation medium, incubated with SAR-20347 (0.5% DMSO) for 20 minutes at 37°C, 5% CO2, and stimulated with individual cytokines. P-STAT levels are measured in duplicate using MSD plates following the manufacturer's instructions (MSD). The IC50 is determined by subtracting background (no cytokine) and relative to DMSO/cytokine control[1]. |
Animal experiment: | Female 7 to 9 week old C57BL/6 mice are used. Mice are administered vehicle or 50 mg/kg SAR-20347 by oral gavage 30 minutes prior to application of 62.5 mg 5% imiquimod cream or control cream. Another dose of vehicle or 50 mg/kg SAR-20347 is given 5.5 hours following the first dose. This treatment is repeated for 5 days and on day 3 and 4, animals are injected with 100 uL saline to prevent dehydration. Each day, the mice are assessed by the same researcher for redness. On the 6th day, the animals are euthanized and photographs are taken[1]. |
References: [1]. Works MG, et al. Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol. 2014 Oct 1;193(7):3278-87. | |
SAR-20347 is an inhibitor of TYK2, JAK1, JAK2 and JAK3 with IC50s of 0.6, 23, 26 and 41 nM, respectively.
When NK-92 cells are stimulated with IL-12, SAR-20347 potently inhibits IL-12-mediated STAT4 phosphorylation, a TYK2-dependent event, with an IC50 of 126 nM. SAR-20347 demonstrates a selectivity of TYK2>JAK1>JAK2>JAK3. Cells without IL-12 in the culture media have no measureable IFN-γ, while cells incubated with IL-12 and SAR-20347 demonstrate dose-dependent inhibition of IFN-γ production. SAR-20347 dose-dependently inhibits the production of secreted embryonic alkaline phosphatase (SEAP) with greatest inhibition occurring with 5 uM of SAR-20347 in these experiments[1].
60 mg/kg SAR-20347 inhibits the production of IFN-γ in the serum by 91% compare to vehicle-treated animals, demonstrating that SAR-20347 can inhibit TYK2 signaling in vivo. SAR-20347 treatment significantly reduces IL-17 production as measured by average signal intensity, consistent with the gene expression analysis[1].
References:
[1]. Works MG, et al. Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol. 2014 Oct 1;193(7):3278-87.
| Cas No. | 1450881-55-6 | SDF | |
| Canonical SMILES | O=C(C1=C(NC2=CC=C(C(N3CCOCC3)=O)C=C2)OC(C4=C(F)C=CC=C4Cl)=N1)N | ||
| 分子式 | C21H18ClFN4O4 | 分子量 | 444.84 |
| 溶解度 | DMSO : 100 mg/mL (224.80 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 | 2.248 mL | 11.24 mL | 22.48 mL |
| 5 mM | 0.4496 mL | 2.248 mL | 4.496 mL |
| 10 mM | 0.2248 mL | 1.124 mL | 2.248 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。