Ponesimod (ACT-128800) 是一种有效的，具有选择性和口服活性的S1P1的激动剂，在放射性配体结合试验中的IC50值为 6 nM。Ponesimod 可高效激活 S1P1介导的信号转导 (EC50=5.7 nM)。Ponesimod 可以预防淋巴细胞介导的组织炎症。
| 生物活性 | Ponesimod (ACT-128800) is a potent, selective and orally active agonist ofS1P1, with anIC50of 6 nM in a radioligand binding assay. Ponesimod activates S1P1-mediated signal transduction with high potency (EC50=5.7 nM). Ponesimod can protect against lymphocyte-mediated tissue inflammation[1][2][3]. |
| IC50& Target | S1PR1 6 nM (IC50) | S1PR3 2068 nM (IC50) | S1PR4 1956 nM (IC50) | S1PR5 142 nM (IC50) |
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体外研究
(In Vitro) | Ponesimod activates human S1P1-5receptors with EC50s of 5.7, >10000, 105, 1108 and 59.1 nM respectively in GTPγS binding assay[2].
Ponesimod activates S1P1receptors with EC50s of 5.7, 1.9, and 1.4 nM for human, rat, and mouse S1P receptors respectively[2].
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体内研究
(In Vivo) | Ponesimod (30 and 175 mg/kg; once daily p.o. for 8 d) prevents delayed-type hypersensitivity in mice[2].
Ponesimod (30 mg/kg by gavage 3 h before and 6 h after adjuvant injection followed by 100 mg/kg/day by administration as food admix for 18 days) prevents adjuvant-induced arthritis in rats[2].
Ponesimod (0.3-100 mg/kg; a single oral gavage) causes a dose-dependent reduction in lymphocyte count, with a plateau effect being reached at 3 mg/kg in rats[2].
Ponesimod (100 mg/kg; once daily oral gavage for 7 d) results in a lymphocyte count reduction to 1900 lymphocytes/μL, and this effect is maintained over the entire 7 days studies. Lymphocyte count returned to baseline levels within 48 h after discontinuation of dosing[2].
| Animal Model: | Female BALB/c mice (15-25 g) sensitized with DNFB[2] | | Dosage: | 30 and 175 mg/kg | | Administration: | Gavage (30 mg/kg) 19 and 3 h before sensitization, followed by administration as food admix (175 mg/kg/day) for 8 days | | Result: | Caused a 60 to 90% reduction of delayed-type hypersensitivity (DTH) parameters of the skin, such as edema, protein extravasation, and neutrophil myeloperoxidase (MPO) activity.
Reduced skin levels of proinflammatory cytokines, such as IL-1β, IL-6, IFNγ, TNFα, and several chemokines to different degrees ranging from -27 to -100%. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(216.93 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.1693 mL | 10.8467 mL | 21.6934 mL | | 5 mM | 0.4339 mL | 2.1693 mL | 4.3387 mL | | 10 mM | 0.2169 mL | 1.0847 mL | 2.1693 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-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: ≥ 2.5 mg/mL (5.42 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.42 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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%corn oil Solubility: ≥ 2.5 mg/mL (5.42 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.42 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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