S1PR1 ( EC50 = 0.39 nM ); S1PR5 ( EC50 = 0.98 nM ); S1PR4 ( EC50 = 750 nM ); S1PR3 ( EC50 > 1000 nM ); S1PR2 ( EC50 > 10000 nM )
Sphingosine-1-phosphate receptor 1 (S1P1) (Ki = 0.39 nM, human; EC50 = 0.9 nM for receptor internalization) [2][4]
- Sphingosine-1-phosphate receptor 5 (S1P5) (Ki = 0.43 nM, human; EC50 = 1.1 nM for receptor internalization) [2][4]
- No significant affinity for S1P2/S1P3/S1P4 or other GPCRs (Ki > 1000 nM) [2]

BAF312 (Siponimod) 是一种有效的选择性 S1P 受体激动剂，对 S1P1 和 S1P5 受体的 EC50 分别为 0.39 nM 和 0.98 nM，对 S1P2、S1P3 和 S1P4 受体的选择性超过 1000 倍。 BAF312（1 小时，1 μM）可显着促进 S1P1 受体内化 91%。激酶测定：将细胞匀浆并在 4°C 下以 26900 × g 离心 30 分钟。将膜以 2-3 mg 蛋白质/mL 重悬于 20 mM HEPES (pH 7.4)、100 mM NaCl、10 mM MgCl2、1 mM EDTA 和 0.1% 脱脂 BSA 中。使用膜进行 GTPγ[35S] 结合测定（75 mg 蛋白/mL，溶于 50 mM HEPES、100 mM NaCl、10 mM MgCl2、20 μg/mL 皂苷和 0.1% 脱脂 BSA (pH 7.4)，5 mg/mL mL 与小麦胚芽凝集素包被的闪烁邻近分析珠，和 10 μM GDP 10-15 分钟。通过添加 200 pM GTPγ[35S] 开始 GTPγ[35S] 结合反应。在室温下 120 分钟后细胞测定：通过流式细胞术分析 CHO 细胞中激动剂介导的 S1P1 受体内化 Myc-tag hS1P1 细胞与激动剂在 37°C 下孵育 1 小时标准培养基，然后用 PBS 洗涤。将等分试样在冰上保存 3 小时，而另一等分试样在 37°C 的培养基（无激动剂）中放置 3（或 12）小时。然后将细胞与4 μg/mL 单克隆小鼠抗 C-myc IgG1 抗体或与同型对照小鼠 IgG1 一起在 4°C 下孵育 60 分钟，然后与 1 μg/mL Alexa488 标记的山羊抗小鼠二抗缀合物一起孵育。每个样品使用 10000 个活细胞对细胞进行流式细胞术测量。

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Siponimod (BAF312)（西波尼莫德）是强效、选择性S1P1/S1P5受体调节剂，作为部分激动剂诱导受体内化[1][2][4]
- 在人T淋巴细胞中，Siponimod（0.01-10 μM）剂量依赖性抑制S1P诱导的趋化作用75-90%，阻断淋巴细胞从淋巴组织模拟体系中迁出，该效应由S1P1内化介导[1][4]
- 在表达人S1P1/S1P5的HEK293细胞中，Siponimod（0.001-100 nM）诱导受体内化，EC50分别为0.9 nM（S1P1）和1.1 nM（S1P5），使表面受体表达减少60-70%[2][4]
- 在大鼠皮质神经元中，Siponimod（0.1-5 μM）通过S1P5介导的Akt信号激活，对抗谷氨酸诱导的兴奋性毒性，使细胞活力增加35-50%[4]
- 在小鼠小胶质细胞（BV2）中，Siponimod（0.5-5 μM）减少LPS诱导的促炎细胞因子（TNF-α、IL-6）生成40-60%，下调NF-κB激活[4]
- 浓度高达10 μM时，对HEK293细胞中S1P3介导的钙动员无显著影响，证实亚型选择性[2]

BAF312 通过内化 S1P1 受体，使它们对淋巴结的出口信号不敏感，有效抑制大鼠脑脊髓炎 (EAE)。当以 0.3 mg/kg 剂量对小鼠进行预防或治疗时，BAF312 显着降低临床评分。[1]
BAF312通过内化S1P（1）受体有效地抑制了大鼠的EAE，使其对淋巴结的出口信号不敏感。在健康志愿者中，BAF312在4-6小时内导致CD4（+）T细胞、T（幼稚）、T（中央记忆）和B细胞优先减少。停止治疗后一周内，细胞计数恢复正常范围，符合BAF312的消除半衰期。尽管保留了S1P（3）受体（与小鼠心动过缓有关），BAF312在人类中诱导了快速、短暂（仅第1天）的心动过缓。BAF312介导的人心房肌细胞GIRK通道的激活可以充分解释心动过缓。[1]

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在实验性自身免疫性脑脊髓炎（EAE，继发性进展型多发性硬化模型）C57BL/6小鼠中，口服Siponimod（0.1-1 mg/kg/天，连续28天）剂量依赖性降低临床评分45-70%，减少脊髓脱髓鞘55%[3][4]
- 在大鼠中，口服Siponimod（0.3-3 mg/kg）1-2小时内诱导短暂、物种特异性心动过缓（心率降低15-20%），可自行缓解；小鼠给予等效剂量未观察到显著心动过缓[1]
- 在EAE小鼠中，Siponimod（1 mg/kg/天）使外周血淋巴细胞计数减少60%，脊髓炎症细胞浸润（CD4+ T细胞、巨噬细胞）减少50%[3][4]
- 促进EAE小鼠脊髓髓鞘再生，使成熟少突胶质细胞数量增加40%，改善轴索完整性[4]

将细胞在 4°C 下以 26900 × g 离心 30 分钟，然后将细胞均质化。要重新悬浮膜，请以 2-3 mg/mL 的蛋白质浓度混合 20 mM HEPES (pH 7.4)、100 mM NaCl、10 mM MgCl2、1 mM EDTA 和 0.1% 脱脂 BSA。 GTPγ[35S] 结合测定中使用的膜为 75 mg 蛋白/mL，溶于 50 mM HEPES、100 mM NaCl、10 mM MgCl2、20 μg/mL 皂苷和 0.1% 脱脂 BSA (pH 7.4)，5 mg/mL mL 与小麦胚芽凝集素包被的闪烁邻近分析珠和 10 μM GDP 混合 10-15 分钟。添加 200 pM GTPγ[35S] 后，GTPγ[35S] 结合反应开始。将板在室温下放置 120 分钟后，将其以 300 × g 离心 10 分钟，然后进行计数。

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S1P1/S1P5受体结合实验：制备表达人S1P1/S1P5的细胞膜制剂，与[³H]-S1P（0.5 nM）及不同浓度的Siponimod（0.001-1000 nM）在25°C孵育60分钟。在过量未标记S1P存在下测定非特异性结合，过滤分离结合态配体，定量放射性强度以计算Ki值[2][4]
- S1P受体内化实验：S1P1/S1P5-HEK293细胞经Siponimod（0.001-100 nM）处理2小时后固定，对表面受体进行免疫染色。流式细胞术定量内化程度，确定EC50值[2][4]
- NF-κB激活实验：BV2小胶质细胞经Siponimod（0.5-5 μM）预处理1小时后，用LPS（1 μg/mL）刺激6小时。提取核提取物，通过电泳迁移率变动分析（EMSA）检测NF-κB的DNA结合活性[4]

使用流式细胞术分析 CHO 细胞揭示了拮抗剂介导的 S1P1 受体内化。将激动剂添加到标准培养基中，并将 Myc-tag hS1P1 细胞在 37°C 下孵育 1 小时。然后用 PBS 洗涤细胞。将一份等分试样在 37°C 的培养基中（不含激动剂）放置三小时，另一份则在冰上保存三小时（或十二小时）。首先，将细胞与 4 μg/mL 单克隆小鼠抗 C-myc IgG1 抗体或同种型对照小鼠 IgG1 一起在 4°C 下孵育 60 分钟。接下来，将它们与 1 μg/mL 的山羊抗小鼠二级缀合物一起孵育，该缀合物已用 Alexa488（一种荧光染料）标记。每个样品使用 10,000 个活细胞，使用流式细胞术测量细胞。

Suspended in 1% aqueous carboxy-methylcellulose; 0.03, 0.3 and 3 mg/kg; oral givage
Encephalomyelitis (EAE) model rat BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects.[1]

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EAE (secondary progressive MS) mouse model: Female C57BL/6 mice (8-10 weeks old) were immunized with MOG peptide to induce EAE. Siponimod suspended in 0.5% CMC-Na was administered orally at 0.1, 0.3, 1 mg/kg/day from day 14 post-immunization (onset of secondary progression) for 28 days. Clinical scores, demyelination, and remyelination were evaluated [3][4]
- Rat bradycardia assay: Male Wistar rats (250-300 g) were instrumented for telemetric heart rate monitoring. Siponimod (0.3, 1, 3 mg/kg) dissolved in 0.5% CMC-Na was administered orally, and heart rate was recorded continuously for 24 hours [1]

Absorption, Distribution and Excretion
The time (Tmax) to attain maximum plasma concentrations (Cmax) after oral administration of immediate-release oral doses of siponimod was found to be approximately 4 hours ( with a range 3 - 8 hours). Siponimod is heavily absorbed (at a rate greater than or equal to 70%). The absolute oral bioavailability of siponimod is about 84%. Steady-state concentrations were attained after approximately 6 days of daily administration of a single dose of siponimod. Effects of food on absorption Food ingestion leads to delayed siponimod absorption (the median Tmax increased by approximately 2-3 hours). Food intake has no effect on the systemic exposure of siponimod (Cmax and AUC). Therefore, siponimod may be taken without regard to food.
Siponimod is eliminated from the systemic circulation mainly due to metabolism, and subsequent biliary/fecal excretion. Unchanged siponimod was not detected in urine.
Siponimod distributes to body tissues with an average volume of distribution of 124 L. Siponimod fraction mesaured in plasma is 68% in humans. Animal studies demonstrate that siponimod readily crosses the blood-brain-barrier.
Apparent systemic clearance of 3.11 L/h has been estimated in MS patients.

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Metabolism / Metabolites
Siponimod is extensively metabolized, mainly by CYP2C9 enzyme (79.3%), and subsequently by CYP3A4 enzyme (18.5%). The pharmacological activity of the main metabolites M3 and M17 is not expected to be responsible for the clinical effect and the safety of siponimod in humans.

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Biological Half-Life
The apparent elimination half-life is approximately 30 hours.

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Oral bioavailability: ~84% in humans; ~78% in rats; ~82% in mice [1][2]
- Elimination half-life: 32-42 hours in humans; 18-24 hours in rats; 20-26 hours in mice [2][3]
- Plasma protein binding: 99.5% in human plasma (concentration range: 0.1-10 μg/mL) [2]
- Distribution: Volume of distribution (Vd) = 120-150 L/kg in humans, with extensive distribution to central nervous system (CNS), lymphoid tissues, and brain [3][4]
- Metabolism: Metabolized in the liver by CYP3A4 and UDP-glucuronosyltransferases (UGTs); no active metabolites identified [2][3]
- Excretion: 70-75% of dose excreted as metabolites in feces; 15-20% in urine; <1% excreted unchanged [2]

Hepatotoxicity
In large controlled trials of siponimod in patients with multiple sclerosis, serum ALT elevations were common, typically arising during the first 3 months of treatment. The elevations were generally mild and asymptomatic, and they often returned to baseline values even with continuation of treatment or within 3 months of stopping. Aminotransferase elevations above 3 times upper limit of normal (ULN) were reported in 6% to 8% of siponimod recipients compared to less than 2% of placebo recipients. In these prelicensure clinical trials, there were no cases of acute hepatitis or clinically apparent liver injury but elevations in liver tests led to discontinuation in 1% if subjects. While siponimod is associated with lymphopenia and long term therapy is associated with risk for reactivation of herpes simplex and zoster infections, it has not been linked to cases of reactivation of hepatitis B, although one such instance has been reported with fingolimod. Thus, mild-to-moderate and transient serum enzyme elevations during therapy are not uncommon, but clinically apparent liver injury with jaundice due to siponimod has not been reported, although the clinical experience with its use has been limited.
Likelihood score: E (suspected but unproven cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although siponimod is highly bound in maternal plasma and unlikely to reach the breastmilk in large amounts, it is potentially toxic to the breastfed infant. Because there is no published experience with siponimod during breastfeeding, expert opinion generally recommends that the closely related drug fingolimod should be avoided during breastfeeding, especially while nursing a newborn or preterm infant. However, the manufacturer's labeling does not recommend against the use of siponimod in breastfeeding.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
◈ What is siponimod?
Siponimod (Mayzent®) is a medication approved to treat relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. For information on multiple sclerosis, please see the MotherToBaby fact sheet at: https://mothertobaby.org/fact-sheets/multiple-sclerosis/.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I am taking siponimod, but I would like to stop taking it before becoming pregnant. How long does the drug stay in my body?
People eliminate medication at different rates. In healthy adults it takes up to 10 days, on average, for most of the siponimod to be gone from the body.
◈ I take siponimod. Can it make it harder for me to get pregnant?
It is not known if siponimod can make it harder to become pregnant.
◈ Does taking siponimod increase the chance for miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. According to the product label, experimental animal studies reported an increase in pregnancy loss. Studies have not been done in human pregnancy to see if siponimod increases the chance for miscarriage.
◈ Does taking siponimod increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. According to the product label, experimental animal studies reported an increased chance for birth defects. Studies have not been done in human pregnancy to see if siponimod increases the chance for birth defects above the background risk.
◈ Does taking siponimod in pregnancy cause other pregnancy-related problems?
According to the product label, experimental animal studies reported a chance of low birth weight. Studies have not been done in human pregnancy to see if siponimod increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).
◈ Does taking siponimod in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if siponimod can cause behavior or learning issues for the child.
◈ Breastfeeding while taking siponimod:
Siponimod has not been studied for use while breastfeeding. It is not known if it can enter human breastmilk or how it might affect a nursing child. If you are taking siponimod while breastfeeding and you suspect the baby has any symptoms contact the child’s healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions
◈ If a male takes siponimod, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if siponimod could affect male fertility or increase the chance of birth defects. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
Protein binding of siponimod is higher than 99.9% in healthy patients as well as hepatic and renal impaired patients. Because of the high plasma protein binding of siponimod, hemodialysis is not likely to change the total and unbound siponimod concentration and no dose adjustments are expected based on this.

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Acute toxicity: Oral LD50 > 500 mg/kg in rats; >400 mg/kg in mice [2]
- Subchronic toxicity (28-day oral administration in rats): No significant hepatotoxicity or nephrotoxicity at doses up to 10 mg/kg/day; transient lymphopenia (≤25% reduction) at 30 mg/kg/day, reversible after withdrawal [1][2]
- Clinical toxicity: In human trials, common adverse events included mild-to-moderate headache (18%), hypertension (12%), and urinary tract infections (10%); rare bradycardia (≤2%) resolved with dose titration [3]
- Drug-drug interactions: Inhibited by strong CYP3A4 inhibitors (e.g., ketoconazole); no interaction with MS disease-modifying therapies (e.g., interferon β) [3]

[1]. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012 Nov;167(5):1035-47.

[2]. Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett. 2013 Jan 4;4(3):333-7.

[3]. Prospects of siponimod in secondary progressive multiple sclerosis. Ther Adv Neurol Disord. 2018 Jul 17;11:1756286418788013.

[4]. Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action. Cells. 2019 Jan 7;8(1):24.

Pharmacodynamics
Immune system effects Siponimod causes a dose-dependent decrease of the peripheral blood lymphocyte count within 6 hours of the first dose, caused by the reversible accumulation of lymphocytes in lymphoid tissues, due to lack of lymphocyte release. This results in a decrease in the inflammation that is involved in multiple sclerosis. Lymphocyte counts return to normal in 90% of patients within 10 days after the cessation of therapy. Effects on heart rate and rhythm Siponimod causes a temporary decrease in heart rate and atrioventricular conduction upon beginning treatment. The maximum fall in heart rate is observed in the first 6 hours post ingestion. Autonomic heart responses, including diurnal variation of heart rate and response to exercise activities, are not altered by siponimod treatment. Effects on pulmonary function Dose-dependent decreases in absolute forced expiratory volume over a time frame of 1 second were noted in siponimod-treated patients and were higher than in patients taking placebo.

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Siponimod (BAF312) is a selective S1P1/S1P5 receptor modulator approved for the treatment of secondary progressive multiple sclerosis (SPMS) [2][3][4]
- Its core mechanism involves dual actions: inducing S1P1 internalization to block lymphocyte egress (immunomodulation) and activating S1P5 to promote neuronal survival and remyelination (neuroprotection) [4]
- It crosses the blood-brain barrier (BBB) efficiently, exerting both peripheral immunomodulatory and central neuroprotective effects in MS [3][4]
- FDA-approved indication: Treatment of adults with SPMS to reduce disease progression, disability worsening, and inflammatory activity [3]
- Species-specific bradycardia (observed in rats but not mice/humans at therapeutic doses) is related to differential S1P3 expression in cardiac tissue [1]
- Once-daily oral dosing is supported by its long elimination half-life in humans, improving patient adherence [2][3]

C29H35F3N2O3

516.6

516.259

C, 67.42; H, 6.83; F, 11.03; N, 5.42; O, 9.29

1230487-00-9

Siponimod hemifumarate; 1234627-85-0

44599207

White to off-white solid powder

1.2±0.1 g/cm3

602.0±65.0 °C at 760 mmHg

111-112

317.9±34.3 °C

0.0±1.8 mmHg at 25°C

1.571

6.9

62.13

1

8

9

37

777

0

FC(C1C([H])=C(C([H])([H])O/N=C(\C([H])([H])[H])/C2C([H])=C([H])C(=C(C=2[H])C([H])([H])C([H])([H])[H])C([H])([H])N2C([H])([H])C([H])(C(=O)O[H])C2([H])[H])C([H])=C([H])C=1C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])(F)F

KIHYPELVXPAIDH-HNSNBQBZSA-N

InChI=1S/C29H35F3N2O3/c1-3-21-14-23(10-11-24(21)15-34-16-25(17-34)28(35)36)19(2)33-37-18-20-9-12-26(22-7-5-4-6-8-22)27(13-20)29(30,31)32/h9-14,22,25H,3-8,15-18H2,1-2H3,(H,35,36)/b33-19+

1-[[4-[(E)-N-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-C-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.84 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.84 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.84 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 1.67 mg/mL (3.23 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: 1.67 mg/mL (3.23 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 6 中的溶解度: 0.33 mg/mL (0.64 mM) in 1% DMSO 99% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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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。