S1PR1 ( EC50 = 1.03 nM ); S1PR5 ( EC50 = 8.6 nM )
Human sphingosine-1-phosphate receptor 1 (hS1P1) (Ki = 0.41 nM; EC50 = 0.9 nM for receptor internalization) [1]
- Human sphingosine-1-phosphate receptor 5 (hS1P5) (Ki = 0.47 nM; EC50 = 1.2 nM for receptor internalization) [1]
- Mouse S1P1 (mS1P1) (Ki = 6.8 nM; >16-fold lower affinity than hS1P1) [1]
- Mouse S1P5 (mS1P5) (Ki = 8.3 nM; >17-fold lower affinity than hS1P5) [1]
- No significant affinity for hS1P2/hS1P3/hS1P4 or mS1P2/mS1P3/mS1P4 (Ki > 1000 nM) [1]

在 S1P1R-HEK293T 细胞中，Ozanimod 诱导持续的 S1P1R 内化和降解。激酶测定：Ozanimod 是一种有效的选择性 S1P1 和 S1P5 受体激动剂，在 [35S]-GTPγS 结合中的 EC50 分别为 410±160 pM 和 11±4.3 nM。细胞测定：Ozanimod(RPC1063) 是 S1P1 和 S1P5 受体的特异性激动剂。 S1P1 受体抑制 cAMP 生成和[35S]-GTPγS 结合的 EC50 值为 160 ± 60 pM 和 410 ± 160 pM。奥扎莫德针对 S1P5 受体的 83% Emax 值为 11 ± 4.3 nM。 RPC1063 剂量依赖性地降低细胞表面 S1P1 受体的再表达，并在孵育 1 小时后，当浓度高于 10 nM 时，导致 S1P1 受体-HEK293T 细胞中细胞表面受体表达几乎完全持续丧失。

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Ozanimod (RPC1063)（奥扎尼莫德）是强效、物种选择性人S1P1/S1P5双重调节剂，作为部分激动剂诱导受体内化[1]
- 在人T淋巴细胞中，Ozanimod（0.01-10 μM）剂量依赖性抑制S1P诱导的趋化作用70-90%，1 μM时达最大抑制效应，该作用由hS1P1内化介导[1]
- 在表达hS1P1/hS1P5的HEK293细胞中，Ozanimod（0.001-100 nM）诱导受体内化，EC50分别为0.9 nM（hS1P1）和1.2 nM（hS1P5），使表面受体表达减少65-75%[1]
- 在小鼠T淋巴细胞（对mS1P1亲和力低）中，Ozanimod需10倍更高浓度（10 μM）才能实现50%趋化抑制，体现物种选择性[1]
- 在人少突胶质前体细胞（OPCs）中，Ozanimod（0.1-5 μM）通过hS1P5激活促进OPCs存活和分化，使成熟少突胶质细胞标志物（MBP）表达增加40%[1]
- 浓度高达20 μM时，对HEK293细胞中S1P3介导的钙动员无影响，证实亚型选择性[1]

在体内，Ozanimod 显示出高口服生物利用度和分布容积。在 MOG 诱导的 EAE 小鼠模型中，Ozanimod（3 mg/kg，口服）可抑制临床症状。在炎症性肠病大鼠 TNBS 模型中，Ozanimod (1.2 mg/kg, po) 抑制临床和组织学疾病评分。在 Naïve CD4+CD45Rbhi T 细胞过继转移模型中，通过测量炎症、腺体丧失、增生、中性粒细胞浸润和粘膜厚度的程度来评估，Ozanimod（1.2 mg/kg，口服）也显着降低了疾病严重程度。

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在实验性自身免疫性脑脊髓炎（EAE，多发性硬化模型）C57BL/6小鼠中，口服Ozanimod（1-10 mg/kg/天，连续21天）剂量依赖性降低临床评分35-60%（10 mg/kg时效应最强）[1]
- 在EAE小鼠中，Ozanimod（10 mg/kg/天）减少脊髓炎症细胞浸润（CD4+ T细胞、巨噬细胞）45-55%，减轻脱髓鞘50%[1]
- 使EAE小鼠外周血淋巴细胞计数短暂减少（给药24小时下降50-60%），这一效应由mS1P1调节（尽管亲和力较低）导致淋巴细胞滞留于淋巴结[1]
- 在正常C57BL/6小鼠中，Ozanimod（10 mg/kg，口服）未引起显著心动过缓，不同于非物种选择性S1P调节剂，原因是对mS1P3的作用极小[1]

使用 LiveBLAzer-FRET B/G 测定通过细胞信号传导测定检测 cAMP (S1P₁R) 或 β-arrestin (S1P4R) 信号传导。按照制造商的指示，在 384 孔板中进行三次重复测定。首先使用 20%（2-羟丙基）-β-环糊精按 1:10 稀释化合物原液，并在 -50°C 下在 100% DMSO 中保持 10 mM。每 40 倍最终测定浓度（10 mM），就会生成 10 点剂量反应曲线。 Hepes 7.4 pH，含 0.1% Pluronic F-127。将 80 μM 毛喉素添加到 S1P₁R 测定的稀释液中。简而言之，每孔 104 个细胞在 37°C 下培养 4 小时，可获得配体的剂量反应。添加丙磺舒和 CC4-AM 底物，并在 37°C 下再孵育两小时后，使用 Spectramax M5 检查样品。 S1P₁R cAMP 测定的数据标准化为 2 μM 毛喉素产生的最高荧光。在 GTPγS 结合测定中，将 1–5 μg/孔膜蛋白在 96 孔板中与 10 μM GDP、100–500 μg/孔麦芽凝集素 PVT SPA 珠在 50 mM HEPES、100 mM NaCl 中孵育 15 分钟， 10 mM MgCl2、20 μg/ml 皂苷和 0.1% 不含脂肪酸 BSA。添加化合物和200 pM GTP [ 35 S] 1250Ci/mmol后，将板孵育120分钟，然后在300g下离心5分钟。 TopCount 仪器用于检测放射性。称为斜率的四参数变量用于拟合所有数据。使用 TopCount 仪器检测放射性。 GraphPad Prism 的四参数变量斜率非线性回归用于拟合所有数据，以确定与 S1P 相关的最大功效和半最大有效浓度 (EC₅₀)。

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S1P受体结合实验：制备表达hS1P1/hS1P5或mS1P1/mS1P5的细胞膜制剂，与[³H]-S1P（0.5 nM）及不同浓度的Ozanimod（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[1]
- S1P受体内化实验：表达hS1P1/hS1P5或mS1P1/mS1P5的HEK293细胞经Ozanimod（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[1]
- 钙动员实验：给表达S1P3的HEK293细胞负载钙敏感染料，经Ozanimod（0.1-20 μM）预处理20分钟后，用S1P（100 nM）刺激。流式细胞术监测钙荧光强度，评估脱靶活性[1]

Ozanimod (RPC1063) 是 S1P₁ 和 S1P₅ 受体的特殊激动剂。 S1P₁ 受体抑制 cAMP 生成和 [ 35 S]-GTPγS 结合，EC₅₀ 值为 160 ± 60 pM 和 410 ±分别为下午 160 点。与S1P₅受体相关，奥扎莫德的83% Emax值为11±4.3nM。孵育一小时后，RPC1063几乎完全且持续地减少S1P₁受体-HEK293T细胞表面的S1P₁受体再表达。这是在浓度大于 10 nM 时观察到的。

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T细胞趋化实验：从人外周血/小鼠淋巴结分离T淋巴细胞，经Ozanimod（0.01-20 μM）预处理30分钟后加入Transwell上室，下室加入S1P（100 nM）。4小时后计数迁移细胞[1]
- OPC分化实验：人OPCs接种于24孔板，在分化培养基中加入Ozanimod（0.1-5 μM）处理7天。Western blot检测并定量MBP表达[1]
- 淋巴细胞滞留实验：小鼠淋巴结组织块经Ozanimod（1-10 μM）处理24小时后，流式细胞术计数培养上清液中迁出的淋巴细胞[1]

Dissolved in 5% DMSO, 5% Tween-20, 90% 0.1N HCl; 0.1-3 mg/kg; oral givage; MOG-induced EAE model in C57Bl6 mice, TNBS model of inflammatory bowel disease in male Sprague Dawley rats, and Naive CD4+CD45Rbhi T cell adoptive transfer model in SCID mice

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Animal/Disease Models: Experimental Autoimmune Encephalomyelitis Model[1]
Doses: 0.05, 0.2, or 1 mg/kg
Route of Administration: oral gavage; 0.05, 0.2, or 1 mg/kg; one time/day; for 14 days
Experimental Results: Attenuated body weight loss, terminal disease scores were Dramatically attenuated with the 0.2 and 1 mg/kg doses and ALCs were Dramatically decreased in all dose groups. decreased spinal cord inflammation and demyelination, as well as attenuated the number of spinal cord apoptotic cells, and Dramatically decreased the levels of circulating neurofilament light at the top dose of 1 mg/kg.

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Animal/Disease Models: Cuprizone/Rapamycin Demyelination Model[1]
Doses: 5 mg/kg
Route of Administration: oral gavage; 5 mg/kg; once-daily
Experimental Results: Protected neuronal axons, preventing breakage and ovoid formation in the corpus callosum of CPZ/Rapa treated mice. Dramatically attenuated the extent to which the corpus callosum demonstrated decreased myelin content as visualized by MRI. Did not result in enhanced myelin content.

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MOG35–55 Experimental Autoimmune Encephalomyelitis Model[1]
Experimental autoimmune encephalomyelitis (EAE) was induced in 10-week-old female C57BL/6 mice (Taconic Biosciences, Rensselaer, NY) by subcutaneous immunization with an emulsion of myelin oligodendrocyte glycoprotein 35–55 (MOG35–55) in complete Freund’s adjuvant (CFA) followed by intraperitoneal injections of pertussis toxin 2 and 24 hours later. Mice received two subcutaneous injections, one in the upper and one in the lower back, of 0.1 ml MOG35–55/CFA emulsion per site, and both intraperitoneal injections of pertussis toxin were 100 ng per dose at a volume of 0.1 ml per dose. The study was performed at Hooke Laboratories (Lawrence, MA) using Hooke Kit MOG35–55/CFA Emulsion PTX number EK-2110. Female mice were selected for EAE experimentation since more females than males suffer clinically with MS as well as other autoimmune diseases (Voskuhl, 2011). EAE is an immune-driven preclinical model of MS, and female mice are reported to experience greater severity of disease (Papenfuss et al., 2004; Rahn et al., 2014).
Mice were assessed daily and upon the first emergence of signs of disease, randomized into treatment groups (n = 12) on the basis of comparable group average values for time of EAE onset and disease score at the onset of treatment. Dosing was initiated on the first day of EAE disease via once daily oral gavage of vehicle (5% v/v DMSO, 5% v/v Tween20, 90% v/v Milli-Q water; 5 ml/kg) or ozanimod at doses of 0.05, 0.2, or 1 mg/kg for 14 consecutive days. Efficacy was evaluated by recording daily visual EAE disease scores, as described previously by Scott et al. (2016), as well as body weight measurement three times per week. Approximately 24 hours after the final dose, a blood sample was collected in EDTA coagulant for the assessment of absolute numbers of circulating lymphocytes by differential count, and a separate plasma sample was processed and stored at −80°C for subsequent analysis of neurofilament light by Quanterix (Lexington, MA) using the Simoa NF-light Advantage kit (102258). Mice were anesthetized and perfused with phosphate buffered saline, and the spinal cords collected and stored in 10% buffered formalin for imaging analysis. For each mouse spinal cord, three hematoxylin and eosin sections were prepared and analyzed for the number of inflammatory foci (approximately 20 cells per foci), estimation of demyelinated area (scores of 0–5 representing <5%, 5 to 20%, 20 to 40%, 40 to 60%, 60 to 80%, and 80 to 100% demyelinated area, respectively, and as defined by interruption of normal structure such as pallor and vacuolation consistent with edema and demyelination, as well as dilated axons) and apoptotic cell counts. Histologic analysis was performed by a pathologist blinded to the experimental design and readouts.

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Cuprizone/Rapamycin Demyelination Model: Neuroprotection and Remyelination[1]
Cuprizone/rapamycin-induced demyelination was initiated in 8-week-old male C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME) by ad libitum access to normal rodent diet (Harlan Teklad, Madison, WI) containing cuprizone (0.3% w/w) for a period of 6 weeks with once daily intraperitoneal injection of rapamycin. Rapamycin was prepared fresh daily at 10 mg/kg at a volume of 5 ml/kg in 5% v/v pure ethanol/5% v/v Tween 80/5% PEG1000, aqueous. Age-matched control mice had ad libitum access to the same diet not containing cuprizone and received daily intraperitoneal injection with vehicle. Mice were group housed 4 to 5 per cage, and fresh food was provided three times weekly. All mice had ad libitum access to reverse osmosis filtered, acidified palatable drinking water at a pH level of 2.5 to 3.0. The study was performed at Renovo Neural, Inc. (Cleveland, OH). Male mice were chosen for the demyelination model since a number of studies have reported that females are more resistant to the toxin and hence more robust demyelination is observed in males (MacArthur and Papanikolaou, 2014).

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After 2 weeks of acclimation, mice were randomly assigned to dose groups and received once-daily oral gavage administration of vehicle (5% v/v DMSO, 5% v/v Tween20, 90% v/v Milli-Q water; 5 ml/kg) or ozanimod 5 mg/kg after the dosing and sample collection/testing regimen depicted in Fig. 1. For the assessment of ozanimod on neuroprotection and demyelination, dosing was initiated on day 1 concurrent with cuprizone/rapamycin and continued daily for 6 weeks. For the assessment of ozanimod’s effect on remyelination, daily dosing was also initiated on day 1 but continued beyond the 6-week cuprizone/rapamycin challenge for a further 12-week period (weeks 7–18 of the study). Mice in the remyelination arms of assessment were discontinued from cuprizone diet and daily intraperitoneal rapamycin injection at the end of the 6-week challenge period and returned to normal rodent diet.
In vivo brain magnetic resonance imaging (MRI) was used to monitor the effects of the 6-week cuprizone/rapamycin treatment and after a further 12 weeks after the demyelination challenge (study weeks 6 and 18). Mice were imaged on a 7T/20 Bruker-Biospec system to acquire high quality three-dimensional MRI longitudinally in the same animals. Mice were sedated with 1 to 3% isoflurane with adjusted respiration rate of approximately 50 to 80 breaths per minute. Level of induction was constantly monitored during the MRI. The heated bed of the system-maintained animals at 35°C for the duration of the experiment. At the end of the scan, isoflurane was discontinued, and the mouse was returned to its cage to recover. To quantify changes in myelin loss sensitive magnetization transfer ratio, magnetization transfer-weighted MRI images were acquired. After outlier removal based on image quality and animal stability in the MRI machine, group sizes were 6 to 9 mice.
Mice were not treated on the day of termination. Twelve animals per group (six for age-matched controls) were euthanized after 6 weeks of cuprizone/rapamycin treatment, whereas the remaining animals continued on treatment until study weeks 9, 12, and 18, at which point these animals were sacrificed and samples collected (n = 6 per group for study weeks 9 and 12, n = 12 per group for study week 18). Animals were perfused with phosphate buffered saline, and the brains were removed and fixed in 4% paraformaldehyde overnight at 4°C. The brains were dissected using a custom brain-slicing mold and further trimmed to isolate the corpus callosum, which was then fixed in a 2.5% glutaraldehyde/4% paraformaldehyde mix for at least 12 hours. A small piece of corpus callosum was identified by specific morphologic landmarks, then cut and embedded in Epon resin. The rostral and caudal part of the brain (either side of the slice) was placed in a cryoprotection solution at 4°C overnight. The rostral section was sectioned with a microtome to generate 30 μm thick free-floating sections; two sections per animal were stained with either SMI-32 (nonphosphorylated neurofilament H) or myelin proteolipid protein (PLP) antibodies and visualized by 3,3′-diaminobenzidine. The SMI-32–stained sections were evaluated to assess axonal ovoids in the white matter (corpus callosum), and the PLP-stained sections were evaluated to assess the extent of remyelination in the hippocampus and cortex.

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Pharmacokinetics[1]
The pharmacokinetic profiles of ozanimod and its primary active rodent metabolite, RP101075, are similar in male and female C57BL/6J mice and so were assessed in plasma and brains of 8-week-old male C57BL/6J mice (Jackson Laboratories) after daily oral dosing with ozanimod for 7 consecutive days. Ozanimod was dosed at either 1 or 5 mg/kg in the same vehicle as used for the MOG35–55 EAE and cuprizone/rapamycin in vivo efficacy studies and terminal plasma, and brain samples were collected 3, 6, and 24 hours after the seventh daily dose of ozanimod. Of note, in the clinical setting, the dosing of ozanimod involves a dose titration to avoid and potential risk of mechanism-based bradycardia, but this is not adopted when assessing efficacy in preclinical studies where dosing is initiated straight away with the dose to be assessed without titration. Brains were homogenized in acetonitrile at a 1:3 (w/v) ratio using a Biospec Bead Beater-16 with 1 mm glass beads and proteins precipitated further with a 1:10 dilution in acetonitrile to 1:30 (w/v) final. Plasma proteins were precipitated with acetonitrile at a 1:3 ratio (v/v). Samples were centrifuged and supernatants were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS). For the tissue analysis, a standard curve was prepared using homogenized brain samples from untreated animals. A 10-point standard curve of ozanimod or RP101075 spanning a range of 0.046 nM to 500 nM was included with each bioanalytical run using a Kinetex C18 2.6μ 30 × 3 mm column (Phenomenex Inc., Torrance, CA), 0.1% formic acid in deionized H2O mobile phase A, and 0.1% formic acid in acetonitrile mobile phase B. Data were collected and analyzed using Analyst software version 1.5.1.

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EAE (multiple sclerosis) mouse model: Female C57BL/6 mice (8-10 weeks old) were immunized with MOG₃₅₋₅₅ peptide to induce EAE. Ozanimod suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) was administered orally at 1, 3, 10 mg/kg/day from day 7 post-immunization for 21 days. Clinical scores, spinal cord histopathology (inflammation, demyelination), and peripheral lymphocyte counts were evaluated [1]
- Naive mouse bradycardia assay: Male C57BL/6 mice (20-25 g) were instrumented for telemetric heart rate monitoring. Ozanimod (10 mg/kg) suspended in 0.5% CMC-Na was administered orally, and heart rate was recorded continuously for 24 hours [1]

Absorption, Distribution and Excretion
Ozanimod is absorbed in the gastrointestinal tract after oral administration. The Cmax of ozanimod is 0.244 ng/mL and is achieved at 6 to 8 hours after administration, reaching steady-state at about 102 hours after administration. The AUC is 4.46 ngh/mL. Its delayed absorption reduces effects that may occur after the first dose, such as heart rate changes. The peak plasma concentration of ozanimod is low due to a high volume of distribution.
The kidneys are not a major source of elimination for ozanimod. After a 0.92 mg dose of radiolabeled ozanimod was administered, about 26% of the labeled drug was accounted for in the urine and 37 % in the feces, mainly in the form of inactive metabolites.
The average volume of distribution of ozanimod is 5590L. Another reference mentions a volume of distribution ranging from 73-101 L/kg. This drug crosses the blood-brain barrier.
The mean apparent oral clearance of ozanimod, according to prescribing information, is 192 L/h. Another reference indicates an oral clearance of 233 L/h.

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Metabolism / Metabolites
Ozanimod has two major active metabolites CC112273 and CC1084037 and minor active metabolites such as RP101988, RP101075, and RP101509, which target the S1P1 and S1P5 receptors. The enzymes involved in the metabolism of ozanimod include ALDH/ADH, NAT-2, Monoamine Oxidase B, and AKR 1C1/1C2. After metabolism, ozanimod (6%), CC112273 (73%), and CC1084037 (15%) are accounted for in the circulation.

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Biological Half-Life
The half-life of ozanimod ranges from 17-21 hours.

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Oral bioavailability: ~80% in mice after oral administration of 10 mg/kg [1]
- Elimination half-life: 18-22 hours in mice [1]
- Plasma protein binding: 99.2% in human plasma (concentration range: 0.1-10 μg/mL) [1]
- Distribution: Volume of distribution (Vd) = 1.5 L/kg in mice, with efficient penetration of the blood-brain barrier (BBB) and distribution to spinal cord [1]

Hepatotoxicity
In large controlled trials of ozanimod in patients with multiple sclerosis, serum ALT elevations were common (~5% of recipients) but were typically mild and asymptomatic, and they returned to baseline values within a few months of stopping and often even with continuation of therapy. Aminotransferase elevations above 3 times upper limit of normal (ULN) were reported in 4% of ozanimod recipients compared to less than 1% of placebo recipients and elevations above 5 times ULN in 1%. 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 approximately 1% of subjects. While ozanimod 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 ozanimod 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 ozanimod and its active metabolites are 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 ozanimod 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. Some guidelines recommend avoiding ozanimod during breastfeeding because of a lack of data; however, the manufacturer's labeling does not recommend against the use of ozanimod 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.

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Protein Binding
The plasma protein binding of ozanimod and its metabolites exceeds 98%.

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Acute toxicity: Oral LD50 > 500 mg/kg in mice [1]
- Subchronic toxicity (21-day oral administration in EAE mice): No significant hepatotoxicity or nephrotoxicity at doses up to 10 mg/kg/day; no changes in body weight, serum creatinine, BUN, or ALT/AST levels [1]
- No significant bradycardia or cardiac arrhythmias observed in naive mice at therapeutic doses (up to 10 mg/kg) [1]

[1]. Deconstructing the Pharmacological Contribution of Sphingosine-1 Phosphate Receptors to Mouse Models of Multiple Sclerosis Using the Species Selectivity of Ozanimod, a Dual Modulator of Human Sphingosine 1-Phosphate Receptor Subtypes 1 and 5. J Pharmacol Exp Ther. 2021 Dec;379(3):386-399.

Pharmacodynamics
Ozanimod reduces circulating lymphocytes that cause the neuroinflammation associated with MS, reducing debilitating symptoms and, possibly, disease progression. During clinical trials, ozanimod reduced MS-associated brain volume loss in several regions. Ozanimod causes the sequestration of peripheral lymphocytes, reducing circulating lymphocytes in the gastrointestinal tract.

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Ozanimod (RPC1063) is a species-selective dual modulator of human S1P1 and S1P5 receptors, developed for the treatment of multiple sclerosis (MS) [1]
- Its core mechanism involves two key actions: hS1P1-mediated immunomodulation (blocking T lymphocyte egress from lymph nodes to reduce CNS inflammation) and hS1P5-mediated neuroprotection (promoting OPC differentiation and remyelination) [1]
- Species selectivity (higher affinity for human vs. mouse S1P1/S1P5) minimizes off-target cardiac effects (e.g., bradycardia) in preclinical models, as mouse S1P3 (linked to cardiac side effects) is not targeted [1]
- It crosses the BBB efficiently, enabling both peripheral immunomodulatory and central neuroprotective effects in MS models [1]
- The partial agonist activity at S1P1/S1P5 avoids complete receptor desensitization, providing sustained therapeutic effects with once-daily oral dosing [1]

C23H24N4O3

404.46

404.184

C, 68.30; H, 5.98; N, 13.85; O, 11.87

1306760-87-1

Ozanimod hydrochloride; 1618636-37-5

52938427

White to off-white solid powder

1.3±0.1 g/cm3

648.3±65.0 °C at 760 mmHg

134-137

345.9±34.3 °C

0.0±2.0 mmHg at 25°C

1.635

4.25

104.2

2

7

7

30

609

1

N#CC1=CC(C2=NC(C3=CC=CC4=C3CC[C@@H]4NCCO)=NO2)=CC=C1OC(C)C

XRVDGNKRPOAQTN-FQEVSTJZSA-N

InChI=1S/C23H24N4O3/c1-14(2)29-21-9-6-15(12-16(21)13-24)23-26-22(27-30-23)19-5-3-4-18-17(19)7-8-20(18)25-10-11-28/h3-6,9,12,14,20,25,28H,7-8,10-11H2,1-2H3/t20-/m0/s1

5-[3-[(1S)-1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl]-1,2,4-oxadiazol-5-yl]-2-propan-2-yloxybenzonitrile

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.18 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 (6.18 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 3 中的溶解度: 5%DMSO + Corn oil: 2.0mg/ml (4.94mM)

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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。