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]

In vitro activity: Ozanimod (RPC-1063) exhibits potency and intrinsic activity of S1P receptor modulators for S1P₅ across species with [ 35 S]-GTPgS binding, with EC₅₀ values of 1.03 nM, 1.29 nM, 0.90 nM, 1.02 nM, and 0.61 nM for Human S1P₁, Cynomolgus monkey S1P₁, Mouse S1P₁, Rat S1P₁, and Canine S1P₁, respectively; and the EC₅₀ values of 8.6 nM, 15.9 nM, 957.5 nM, 2032.7 nM, and 1662.0 nM for Human S1P₅, Cynomolgus monkey S1P₅, Mouse S1P₅, Rat S1P₅, and Canine S1P₅,[1].
Ozanimod restores the potency with an EC₅₀ for mS1P₅ from 958 nM to 6.7 nM for mS1P₅_A120T, which closely resembles the EC₅₀ for hS1P₅ of 8.6 nM by altering the alanine in the mouse sequence[1].
Ozanimod exhibits a binding affinity for hS1P₅, mS1P₅, and mS1P₅ _A120T, with corresponding K_i values of 2.0 nM, 59.9 nM, and 5.6 nM[1].
Ozanimod has saturation binding for [3H]-ozanimod to hS1P₅, mS1P₅_A120T, and K_D values of 6.56 nM and 7.35 nM, respectively. It also has saturation binding for [3H]-A971432 to S1P₅D value of 8.75 nM[1].

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Ozanimod (RPC1063) is a potent, species-selective dual modulator of human S1P1 and S1P5 receptors, acting as a partial agonist and inducing receptor internalization [1]
- In human T lymphocytes, Ozanimod (0.01-10 μM) dose-dependently inhibited S1P-induced chemotaxis by 70-90%, with maximal inhibition at 1 μM, via hS1P1 internalization [1]
- In hS1P1/hS1P5-expressing HEK293 cells, Ozanimod (0.001-100 nM) induced receptor internalization with EC50 values of 0.9 nM (hS1P1) and 1.2 nM (hS1P5), reducing surface receptor expression by 65-75% [1]
- In mouse T lymphocytes (low affinity for mS1P1), Ozanimod required 10-fold higher concentration (10 μM) to achieve 50% chemotaxis inhibition, reflecting species selectivity [1]
- In human oligodendrocyte precursor cells (OPCs), Ozanimod (0.1-5 μM) promoted OPC survival and differentiation via hS1P5 activation, increasing mature oligodendrocyte marker (MBP) expression by 40% [1]
- It had no effect on S1P3-mediated calcium mobilization in HEK293 cells at concentrations up to 20 μM, confirming subtype selectivity [1]

Ozanimod (RPC-1063) (oral gavage; 0.05, 0.2, or 1 mg/kg; once daily; for 14 consecutive days) exposures sufficient to engage S1P₁, but not S1P₅, lead to decreased levels of circulating lymphocytes, disease scores, and body weight loss; lessen the number of apoptotic cells, inflammation, and demyelination in the spinal cord; and decrease the amount of neurofilament light, a marker of neuronal degeneration, in circulation[1].
Ozanimod (oral gavage; 5 mg/kg; once-daily) does not promote enhanced remyelination following intoxication, but it does stop axonal degradation and myelin loss during toxin challenge[1].
Ozanimod (oral, 1 or 5 mg/kg, for 7 days) exhibits favorable pharmacoK_inetics in mice[1].

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In C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE, multiple sclerosis model), oral Ozanimod (1-10 mg/kg/day for 21 days) dose-dependently reduced clinical scores by 35-60% (maximal effect at 10 mg/kg) [1]
- In EAE mice, Ozanimod (10 mg/kg/day) reduced spinal cord inflammatory cell infiltration (CD4+ T cells, macrophages) by 45-55% and attenuated demyelination by 50% [1]
- It induced a transient reduction in peripheral blood lymphocyte counts (50-60% decrease at 24 hours post-dosing) in EAE mice, due to lymphocyte sequestration in lymph nodes via mS1P1 modulation (despite lower affinity) [1]
- In naive C57BL/6 mice, Ozanimod (10 mg/kg, p.o.) did not cause significant bradycardia, unlike non-species-selective S1P modulators, due to minimal mS1P3 interaction [1]

The cAMP (S1P₁R) or β-arrestin (S1P4R) signaling was detected by cell signaling assays using the LiveBLAzer-FRET B/G assay. As directed by the manufacturer, assays are carried out in triplicate in 384-well plates. Twenty percent (2-hydoxypropyl)-β-cyclodextrin is used to dilute compound stocks 1:10 at first, and they are kept at 10 mM in 100% DMSO at -50°C. For every 40 times the final assay concentration in 10 mM, a 10-point dose response curve is generated. Hepes 7.4 pH with 0.1% Pluronic F-127. 80 μM forskolin is added to the diluent for the S1P₁R assay. To put it briefly, 104 cells per well are cultured for 4 hours at 37°C with a dose response of ligand available. Probenecid and CC4-AM substrate are added, and after an additional two hours of incubation at 37°C, the sample is examined using a Spectramax M5. Data for S1P₁R cAMP assays is normalized to the highest fluorescence produced by 2 μM forskolin. In GTPγS binding assays, 1–5 μg/well of membrane protein is incubated for 15 minutes in 96-well plates with 10 μM GDP, 100–500 μg/well Wheat Germ Agglutinin PVT SPA beads in 50 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 20 μg/ml saponin, and 0.1% fatty acid free BSA. The plates are incubated for 120 minutes after the addition of compound and 200 pM GTP [ 35 S] 1250Ci/mmol, and then centrifuged for 5 minutes at 300g. A TopCount Instrument is used to detect radioactivity. A four-parameter variable called slope is used to fit all of the data. Radioactivity is detected with a TopCount Instrument. GraphPad Prism's four parameter variable slope non-linear regression is used to fit all the data in order to determine the maximum efficacy and half-maximum effective concentration (EC₅₀) in relation to S1P.

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S1P receptor binding assay: Membrane preparations from hS1P1/hS1P5 or mS1P1/mS1P5-expressing cells were incubated with [³H]-S1P (0.5 nM) and Ozanimod (0.001-1000 nM) at 25°C for 60 minutes. Non-specific binding was determined with excess unlabeled S1P. Bound ligands were separated by filtration, and radioactivity was quantified to calculate Ki values [1]
- S1P receptor internalization assay: hS1P1/hS1P5 or mS1P1/mS1P5-HEK293 cells were treated with Ozanimod (0.001-100 nM) for 2 hours, fixed, and immunostained for surface receptors. Internalization was quantified by flow cytometry to determine EC50 values [1]
- Calcium mobilization assay: S1P3-HEK293 cells were loaded with calcium-sensitive dye, pretreated with Ozanimod (0.1-20 μM) for 20 minutes, then stimulated with S1P (100 nM). Calcium fluorescence intensity was monitored by flow cytometry to assess off-target activity [1]

Ozanimod (RPC1063) was a particular agonist for S1P₁ and S1P₅ receptors. The suppression of cAMP generation and [ 35 S]-GTPγS binding by S1P₁ receptors had EC₅₀ values of 160 ± 60 pM and 410 ± 160 pM, respectively. In relation to the S1P₅ receptor, ozanimod's 83% Emax value was 11 ± 4.3 nM. After one hour of incubation, RPC1063 virtually completely and persistently reduced S1P₁ receptor re-expression on the cell surface in S1P₁ receptor-HEK293T cells. This was observed at concentrations greater than 10 nM.

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T cell chemotaxis assay: Human/mouse T lymphocytes were isolated from peripheral blood/lymph nodes, pretreated with Ozanimod (0.01-20 μM) for 30 minutes, and added to Transwell upper chambers. S1P (100 nM) was added to lower chambers, and migrated cells were counted after 4 hours [1]
- OPC differentiation assay: Human OPCs were seeded in 24-well plates, treated with Ozanimod (0.1-5 μM) for 7 days in differentiation medium. MBP expression was detected by Western blot and quantified [1]
- Lymphocyte sequestration assay: Mouse lymph node explants were treated with Ozanimod (1-10 μM) for 24 hours, and egressed lymphocytes in culture supernatants were counted by flow cytometry [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 via the gastrointestinal tract after oral administration. The peak plasma concentration (Cmax) of ozanimod is 0.244 ng/mL, reached 6 to 8 hours after administration, and steady state is reached in approximately 102 hours. The AUC is 4.46 ng/mL. This delayed absorption may reduce potential adverse reactions after the first dose, such as changes in heart rate. Due to its large volume of distribution, ozanimod has a relatively low peak plasma concentration. The kidneys are not the primary route of excretion for ozanimod. After administration of 0.92 mg of radiolabeled ozanimod, approximately 26% of the labeled drug is excreted in the urine and 37% in the feces, primarily as inactive metabolites. The mean volume of distribution of ozanimod is 5590 L. Another reference mentions a volume of distribution range of 73–101 L/kg. The drug can cross the blood-brain barrier.
According to prescribing information, the mean apparent oral clearance of ozanimod is 192 L/h. Another reference indicates an oral clearance of 233 L/h.
Metabolism/Metabolites
Ozanimod has two major active metabolites, CC112273 and CC1084037, as well as several minor active metabolites, such as RP101988, RP101075, and RP101509, which target the S1P1 and S1P5 receptors. Enzymes involved in the metabolism of ozanimod include ALDH/ADH, NAT-2, monoamine oxidase B, and AKR 1C1/1C2. After metabolism, the circulatory system mainly contains ozanimod (6%), CC112273 (73%), and CC1084037 (15%).

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Biological half-life
The half-life of ozanimod is 17-21 hours.

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Oral bioavailability: Approximately 80% after oral administration of 10 mg/kg to mice [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) in mice = 1.5 L/kg, effectively crossing the blood-brain barrier (BBB) and distributing to the spinal cord [1]

Hepatotoxicity
In large controlled ozanimod trials in patients with multiple sclerosis, elevated serum ALT levels were common (approximately 5% of participants), but were usually mild and asymptomatic, returning to baseline levels within months of discontinuation, and often even with continued treatment. In the ozanimod group, 4% of participants experienced transaminase elevations exceeding 3 times the upper limit of normal (ULN), compared to less than 1% in the placebo group; 1% of participants experienced transaminase elevations exceeding 5 times the ULN. No cases of acute hepatitis or clinically significant liver injury occurred in these premarket clinical trials, but approximately 1% of participants discontinued treatment due to abnormal liver function tests. While ozanimod is associated with lymphopenia and long-term treatment is associated with a risk of relapse of herpes simplex and herpes zoster virus infections, it has not been found to be associated with hepatitis B virus relapse, although one case of hepatitis B virus relapse has been reported with fingolimod. Therefore, mild to moderate transient increases in serum enzymes during treatment are not uncommon, but there have been no reports of clinically significant liver injury with jaundice caused by ozanimod, despite limited clinical experience.
Probability Score: E (Suspected but not confirmed cause of clinically significant liver injury).
Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
Although ozanimod and its active metabolites are highly bound in maternal plasma and unlikely to enter breast milk in large quantities, it still poses potential toxicity to breastfed infants. Due to the lack of published experience regarding the use of ozanimod during lactation, expert opinion generally recommends avoiding the use of fingolimod, a drug closely related to it, during lactation, especially in newborns or preterm infants. Some guidelines recommend avoiding ozanimod during lactation due to a lack of data; however, the manufacturer's label does not recommend that ozanimod be contraindicated in breastfeeding women.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding
Plasma protein binding of ozanimod and its metabolites exceeds 98%.

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Acute toxicity: Oral LD50 in mice > 500 mg/kg [1]
- Subchronic toxicity (21-day oral administration in EAE mice): No significant hepatotoxicity or nephrotoxicity was observed at doses up to 10 mg/kg/day; no changes were observed in body weight, serum creatinine, blood urea nitrogen, or ALT/AST levels [1]
- At therapeutic doses (up to 10 mg/kg), no significant bradycardia or arrhythmia was observed in untreated mice [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, thereby alleviating neuroinflammation associated with multiple sclerosis (MS), thus reducing frailty symptoms and potentially slowing disease progression. In clinical trials, ozanimod reduced MS-related brain volume loss in multiple regions. Ozanimod causes peripheral lymphocyte retention, thereby reducing circulating lymphocytes in the gastrointestinal tract.

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Ozanimod (RPC1063) is a species-selective dual regulator that acts on human S1P1 and S1P5 receptors for the treatment of multiple sclerosis (MS) [1]
- Its core mechanism involves two key roles: hS1P1-mediated immunomodulation (blocking T lymphocyte migration from lymph nodes to reduce central nervous system inflammation) and hS1P5-mediated neuroprotection (promoting oligodendrocyte precursor differentiation and myelin regeneration) [1]
- Species selectivity (higher affinity for human S1P1/S1P5 than for mice) minimizes off-target cardiac effects (e.g., bradycardia) in preclinical models because mouse S1P3 (associated with cardiac side effects) is not its target [1]
- It can effectively cross the blood-brain barrier to exert peripheral immunomodulatory and central neuroprotective effects in multiple sclerosis models [1]
- The partial agonist activity of S1P1/S1P5 avoids complete receptor desensitization, thus providing sustained therapeutic effects through once-daily oral administration [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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 5%DMSO + Corn oil: 2.0mg/ml (4.94mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)