S1P1 agonist 7

S1P1激动剂7（化合物28）的分子对接研究表明，与芬戈莫德相比，其对β受体阻滞剂的抑制作用增强了4.51倍，G蛋白信号通路EC50值为12.7 nM，β受体阻滞剂募集EC50值为3.23 nM [1]。S1P1激动剂7（1-10 µM，15-60 min）在所有人类、大鼠和小鼠的肝微粒体中均表现出较高的稳定性，并且在10 µM浓度下对大多数CYP同工酶没有显著的抑制作用 [1]。 S1P1激动剂7（起始浓度100 μM，经系列稀释，作用90分钟）在Chem-4/G15和CHO-K1 EDG1细胞模型中对S1P1受体表现出高度选择性，其G蛋白信号传导的EC50为0.014 μM，β-阻遏蛋白募集的EC50为0.0023 μM，而对S1P5受体的活性较弱[1]。S1P1激动剂7（0.041–10 μM，作用2分钟）即使在最高测试浓度下，也未引起人iPSC来源心肌细胞峰值频率或搏动频率的任何可观察变化[1]。

S1P1 agonist 7 (1、3 和 10 mg/kg，灌胃，单次喷雾) 可降低 C57BL/6N 小鼠的外周血复制计数[1]。 S1P1 agonist 7 (10 mg/kg，灌胃，每日一次，连续 23 天) 在 MOG35-55 诱导的 EAE小鼠模型中表现出强大的保护作用，能够阻断其疾病影响、抑制疾病进展并减弱相关的病理损伤[1]。

Animal/Disease Models: Female C57BL/6N mice (8 weeks old) immunized with MOG/CFA emulsion and received PTX on two consecutive days to induce EAE[1]
Doses: 10 mg/kg
Route of Administration: i.g., daily for 23 days
Experimental Results: Delayed disease onset and reduced symptom severity, as indicated by lower cumulative and mean maximum clinical scores. Maintained its prophylactic effect until the peak of disease severity, which occurred around 17 dpi. Prevented body weight loss and lowered disease incidence in EAE mice, indicating a protective effect. Moderated disease progression, and led to a steady reduction in symptom severity until 34 dpi, demonstrating a moderate therapeutic effect comparable to that of Siponimod. Significantly reduced the cumulative clinical score from 19 dpi (the peak of EAE) to 34 dpi. Prevented body weight loss compared to the vehicle-treated group. Markedly reduced demyelination in the spinal cord's dorsal column and ventral white matter. Reduced immune cell infiltration and partially preserved myelin integrity.

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Animal/Disease Models: Female C57BL/6N mice (8 weeks old)[1]
Doses: 1, 3, and 10 mg/kg
Route of Administration: i.g., single dose
Experimental Results: Reduced PLC to 24.4 % of baseline at 4 h post administration, outperforming Fingolimod (36.3 %). Promoted a rapid recovery of PLCs to 70.8 % of baseline within 28 hours, in contrast to Fingolimod, which causes prolonged lymphopenia. Produced a rapid reduction in lymphocyte counts to approximately 40 % of baseline at 3 h post administration and achieved maximal suppression at the 3 and 10 mg/kg doses by 6 h post administration, while triggering an early rebound in the 1 mg/kg group by the same time, suggesting the onset of recovery. Elicited a stronger pharmacodynamic response at 3 and 10 mg/kg, and permitted full lymphocyte recovery in all groups within 24 hours.

C23H22N2O5

406.43

Typically exists as solids at room temperature

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。