Siponimod (BAF-312) 是一种口服有效、选择性的鞘脂S1P受体调节剂。Siponimod 对S1P1和S1P5受体的选择性高于 S1P2、S1P3和 S1P4，EC50分别为 0.39，0.98，>10000，>1000 和 750 nM。Siponimod 可用于多发性硬化症 (MS) 的研究。
| 生物活性 | Siponimod (BAF-312) is an orally active and selectivesphingosine-1-phosphate(S1P) receptor modulator. Siponimod is selective forS1P1andS1P5over S1P2, S1P3, and S1P4, withEC50s of 0.4, 0.98, >10000, >1000, and 750 nM, respectively. Siponimod can be used for multiple sclerosis (MS) research[1]-[4]. |
| IC50& Target | S1PR1 0.39 nM (EC50) | S1PR5 0.98 nM (EC50) | S1PR4 750 nM (EC50) | S1PR3 >1000 nM (EC50) | S1PR2 >10000 nM (EC50) |
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体外研究
(In Vitro) | Siponimod (compound 32) exhibits selectivity to S1P1and S1P5, and spares activity on the S1P2, S1P3 and S1P4 receptors[1].
Siponimod (1 mM; 0-1 h) promotes internalization of S1P1 receptors, results 94% S1P1 receptors localized intracellularly at 1 h[2].
Siponimod (0.001 nM-1 μM; 1 h) activates the GIRK channel in atrial myocytes, with an EC50value of 15.8 nM in CHO cell line CCL-61[2].
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体内研究
(In Vivo) | Siponimod (1 g/kg; i.v.; single dose) shows low to moderate in monkey, but high in rat in metabolism studies with liver microsomes. The absolute bioavailability is 50 and 71% in the rat and monkey, respectively, indicating no major presystemic first pass metabolism[1].
Siponimod (0.3, 3 mg/kg; p.o.; once daily; 23 d) suppresses experimental autoimmune encephalomyelitis (EAE) in rats by internalizing S1P1 receptors[2].
Parmacokinetics of Siponimod in rats and monkey[1]
| /td> | CL (L/h/kg) | Vss(L/kg) | T1/2(h) | F (%) | | Rat | 0.36 | 2.15 | 6 | 50 | | Monkey | 0.098/td> | 2.12 | 19 | 71 |
| Animal Model: | Experimental autoimmune encephalomyelitis (EAE) model in Lewis rats (200-250 g)[2] | | Dosage: | 0.03, 0.3, 3 mg/kg | | Administration: | Oral gavage; once daily; 23 days | | Result: | Decreased peripheral lymphocyte counts by 88% at the Tmaxof 8 h postadministration. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : ≥ 30 mg/mL(58.07 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.9357 mL | 9.6787 mL | 19.3573 mL | | 5 mM | 0.3871 mL | 1.9357 mL | 3.8715 mL | | 10 mM | 0.1936 mL | 0.9679 mL | 1.9357 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)。-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 (4.84 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.84 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% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.84 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.84 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 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (4.84 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.84 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。 4. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: 1.67 mg/mL (3.23 mM); Suspended solution; Need ultrasonic 5. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: 1.67 mg/mL (3.23 mM); Suspended solution; Need ultrasonic 6. 请依序添加每种溶剂： 1% DMSO 99% saline Solubility: 0.33 mg/mL (0.64 mM); Suspended solution; Need ultrasonic *以上所有助溶剂都可在本网站选购。
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