• 产品描述： Enpatoran (M5049) is a potent, orally active and dual TLR7/8 inhibitor with IC50s of 11.1 nM and 24.1 nM in HEK293 cells, respectively. Enpatoran is inactive against TLR3, TLR4 and TLR9. Enpatoran can block molecule synthetic ligands and natural endogenous RNA ligands. Enpatoran exhibits excellent pharmacokinetic properties in vivo. Enpatoran can be used for both innate and adaptive autoimmunity blocking research

• 靶点： TLR7:11.1 nM (IC50, in HEK293 cells);TLR8:24.1 nM (IC50, in HEK293 cells);TLR7:68.3 nM (IC50, in peripheral blood mononuclear cells (PBMCs));TLR8:620 nM (IC50, in peripheral blood mononuclear cells (PBMCs));TLR7:2.2 nM (IC50, in whole blood (WB) cells);TLR8:120 nM (IC50, in whole blood (WB) cells);TLR

• 体外研究：
  Enpatoran (0.01 nM-10 μM) 抑制由所有配体 (miR-122、Let7c RNA、Alu RNA 和 R848) 刺激的 IL-6 的产生，IC50 值范围为 35 - 45 nM

• 体内研究：
  在 R848 (腹腔注射 25 μg) 之前使用 Enpatoran (M5049；口服灌胃；1 mg/kg) 预处理可剂量依赖性地抑制小鼠体内 IL-6 和 IFN-α 的产生。 Enpatoran (M5049) 在口服给药 (小鼠、大鼠和狗 1.0 mg/kg) 后表现出高口服生物利用度 (小鼠 100%，大鼠 87%，狗 84%)。 Enpatoran（小鼠、大鼠和犬 1.0 mg/kg；iv）由于具有高血浆清除率（分别为 1.4、1.2 和 0.59 L/h/kg）以及大分布容积（分别为 2.7、8.7 和 5.7 L/ kg），表现出中等的半衰期（小鼠 1.4，大鼠 5.0 和狗 13 小时）。 Animal Model: Female C57BL/6 mice Dosage: 0.1 mg/kg and 1 mg/kg Administration: Oral gavage; administered 1 hour prior to R848 challenge Result: The TLR7/8 agonist R848 stimulated both IFN-α and IL-6 production in mice.Enpatoran decreased IFN-α and IL-6 production stimulated by R848. Animal Model: Female CD1 mice, Female Wistar rats, Female beagle dogs Dosage: 1 mg/kg (Pharmacokinetic Analysis) Administration: Intravenous (i.v.) or oral gavageResult: T1/2s of 1.4, 5.0 and 13 h for mice, rats and dogs, respectively.

• 参考文献：
  1. Jaromir Vlach, et al. Discovery of M5049: A Novel Selective TLR7/8 Inhibitor for Treatment of Autoimmunity. J Pharmacol Exp Ther. 2020 Dec 16;JPET-AR-2020-000275.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	3.122 ml	15.609 ml	31.219 ml
  5 mM	0.624 ml	3.122 ml	6.244 ml
  10 mM	0.312 ml	1.561 ml	3.122 ml
  50 mM	0.062 ml	0.312 ml	0.624 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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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 *