Enpatoran (M5049) 是一种有效的、具有口服活性的TLR7/8抑制剂，在HEK293 细胞中，其IC50s 分别为 11.1 nM 和 24.1 nM。Enpatoran 对 TLR3, TLR4 和 TLR9 无活性。Enpatoran 可以阻断分子合成配体和天然内源性 RNA 配体。Enpatoran 在体内的表现出良好的药代动力学特性。Enpatoran 可用于先天性和适应性自身免疫阻断的相关研究。
| 生物活性 | Enpatoran (M5049) is a potent, orally active and dualTLR7/8inhibitor withIC50s of 11.1 nM and 24.1 nM in HEK293 cells, respectively. Enpatoran is inactive againstTLR3,TLR4andTLR9. Enpatoran can block molecule synthetic ligands and natural endogenous RNA ligands. Enpatoran exhibits excellent pharmacokinetic propertiesin vivo. Enpatoran can be used for both innate and adaptive autoimmunity blocking research[1]. |
| IC50& Target[1] | 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) |
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体外研究
(In Vitro) | Enpatoran (0.01 nM-10 μM) inhibits production of IL-6 stimulated by all the ligands (miR-122, Let7c RNA, Alu RNA, and R848) with IC50values ranging from 35 to 45 nM[1].
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体内研究
(In Vivo) | Pre-treatment with Enpatoran (M5049; oral gavage; 1 mg/kg) before R848 (intraperitoneal injection of 25 μg) dose-dependently inhibits the production of IL-6 and IFN-α in mice[1].
Enpatoran (M5049) exhibits high oral bioavailability (mouse 100%, rat 87%, dog 84%) following oral administration (mouse, rat and dog 1.0 mg/kg)[1].
Enpatoran exhibits moderate half-lives (mouse 1.4, rat 5.0 and dog 13 h) due to high plasma clearance (1.4, 1.2 and 0.59 L/h/kg, respectively) combined with large volumes of distribution (2.7, 8.7 and 5.7 L/kg, respectively) following intravenous administration (mouse, rat and dog 1.0 mg/kg)[1].
| Animal Model: | Female C57BL/6 mice[1] | | 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[1] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | Intravenous (i.v.) or oral gavage | | Result: | T1/2s of 1.4, 5.0 and 13 h for mice, rats and dogs, respectively. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 24.44 mg/mL(76.30 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1220 mL | 15.6099 mL | 31.2198 mL | | 5 mM | 0.6244 mL | 3.1220 mL | 6.2440 mL | | 10 mM | 0.3122 mL | 1.5610 mL | 3.1220 mL |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.44 mg/mL (7.62 mM); Clear solution
此方案可获得 ≥ 2.44 mg/mL (7.62 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 24.4 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.44 mg/mL (7.62 mM); Clear solution
此方案可获得 ≥ 2.44 mg/mL (7.62 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 24.4 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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