• 产品描述： SAR-20347 is an inhibitor of TYK2, JAK1/2/3 (IC50: 0.6/23/26/41 nM).

• 靶点： JAK; Tyrosine Kinases;TyrosineKinases; JAK

• 体外研究：
  SAR-20347 effectively inhibits IL-12-mediated STAT4 phosphorylation (TYK2-dependent, IC50: 126 nM) when NK-92 cells are stimulated with IL-12. In the culture media, cells without IL-12 have no measurable IFN-γ, while cells incubated with IL-12 and SAR-20347 demonstrate dose-dependent inhibition of IFN-γ production. SAR-20347 (maximum effect: 5 μM) dose-dependently inhibits the production of secreted embryonic alkaline phosphatase (SEAP).

• 体内研究：
  Compared to vehicle-treated animals, SAR-20347 (60 mg/kg) inhibits the production of IFN-γ in the serum by 91%, demonstrating that SAR-20347 can inhibit TYK2 signaling in vivo. SAR-20347 markedly reduces IL-17 production as measured by average signal intensity, consistent with the gene expression analysis.

• 细胞实验： 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).

• 动物实验： 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. On the 6th day, the animals are euthanized and photographs are taken.

• 参考文献：
  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. 2. Kang X, Yang M, Shi Y, et al. Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors[J]. Cell Communication and Signaling. 2018 Jul 20;16(1):42.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.248 ml	11.24 ml	22.48 ml
  5 mM	0.45 ml	2.248 ml	4.496 ml
  10 mM	0.225 ml	1.124 ml	2.248 ml
  50 mM	0.045 ml	0.225 ml	0.45 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *