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Identification
- Summary
Ozanimod is a sphingosine 1-phosphate receptor modulator being studied to treat Multiple Sclerosis (MS) and inflammatory bowel disease (IBD).
- Brand Names
- Zeposia, Zeposia 7-day Starter Pack, Zeposia Starter Kit
- Generic Name
- Ozanimod
- DrugBank Accession Number
- DB12612
- Background
Ozanimod is a once-daily sphingosine 1-phosphate receptor modulator for the treatment of relapsing Multiple Sclerosis (MS) and inflammatory bowel disease. It was developed by Celgene (now acquired by Bristol-Myers Squibb) 9 and was approved by the FDA on March 26, 2020.10,11 The US approval was followed by the approval in Canada on October 2, 2020.14 In November 2021, ozanimod was also approved by the European Commission for the treatment of adults with relapsing remitting multiple sclerosis.12,13
MS is a devastating inflammatory disease that often progresses and causes severe neurological, physical, and cognitive effects.4 Inflammatory bowel disease also a chronic inflammatory condition and can cause persistent abdominal pain, diarrhea, bloody stools, and vomiting.5
In clinical trials, Ozanimod has been shown to be well-tolerated and has resulted in a higher decrease in the rate of MS relapses than with intramuscular interferon beta-1a, a current standard in MS therapy. Studies involving patients with inflammatory bowel disease have also shown promising results.1,6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ozanimod (DB12612)
- Weight
- Average: 404.47
Monoisotopic: 404.184840649 - Chemical Formula
- C23H24N4O3
- Synonyms
- Ozanimod
- Ozanimodum
- External IDs
- RPC 1063
- RPC-1063
- RPC1063
Pharmacology
- Indication
Ozanimod is a sphingosine 1-phosphate receptor modulator indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is also used to treat moderately to severely active ulcerative colitis (UC) in adults.11,13,14
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Clinically isolated syndrome (cis) •••••••••••• ••••••• Management of Moderately to severely active ulcerative colitis •••••••••••• ••••• •••••••••• •••••••• •• •••••••••••• ••••••• ••••••• Management of Moderately to severely active ulcerative colitis •••••••••••• ••••• ••••••• Treatment of Progressive multiple sclerosis (pms) •••••••••••• ••••••• Management of Relapsing forms of multiple sclerosis •••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.1,11 Ozanimod causes the sequestration of peripheral lymphocytes, reducing circulating lymphocytes in the gastrointestinal tract.7
- Mechanism of action
Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system.2,7 S1P can be expressed ubiquitously, playing an important role in regulating inflammation. S1P1R, S1P2R, and S1P3R receptors can be found in the cardiovascular, immune, and central nervous systems. S1P4R is found on lymphocytic and hematopoietic cells, while S1P5R expression is found only on the spleen (on natural killer cells) or in the central nervous system.3
Ozanimod is a selective modulator of S1P receptors and binds to S1P1R and S1P5R subtypes.3 The mechanism of action of ozanimod is not fully understood, but this drug likely reduces the migration of lymphocytes that usually aggravate the inflammation associated with MS.11
Target Actions Organism ASphingosine 1-phosphate receptor 1 agonistHumans ASphingosine 1-phosphate receptor 5 agonistHumans - Absorption
Ozanimod is absorbed in the gastrointestinal tract after oral administration. The Cmax of ozanimod is 0.244 ng/mL11 and is achieved at 6 to 8 hours after administration7, reaching steady-state at about 102 hours after administration. The AUC is 4.46 ng*h/mL.11 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.7
- Volume of distribution
The average volume of distribution of ozanimod is 5590L.11 Another reference mentions a volume of distribution ranging from 73-101 L/kg.2 This drug crosses the blood-brain barrier.7
- Protein binding
The plasma protein binding of ozanimod and its metabolites exceeds 98%.11
- Metabolism
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.11
Hover over products below to view reaction partners
- Route of elimination
The kidneys are not a major source of elimination for ozanimod.2 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.11
- Half-life
- Clearance
The mean apparent oral clearance of ozanimod, according to prescribing information, is 192 L/h.11 Another reference indicates an oral clearance of 233 L/h.2
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Overdose and LD50 information for ozanimod is not readily available in the literature.2,8,11 The NOAEL dose is 0.164 mg/kg/d for monkeys, and the human equivalent dose to this is about 0.053 mg/kg/day.2 An overdose of this drug likely results in adverse effects such as somnolence, fatigue, headache, dizziness, bradyarrhythmia, cardiac conduction defects, hypertension, liver injury, and nausea.2,11
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Ozanimod. Abemaciclib Abemaciclib may decrease the excretion rate of Ozanimod which could result in a higher serum level. Abiraterone The metabolism of Ozanimod can be decreased when combined with Abiraterone. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ozanimod. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Ozanimod. - Food Interactions
- Avoid tyramine-containing foods and supplements. Avoid food containing high amounts of tyramine (>150mg) as these may increase the risk of hypertension when taken with ozanimod.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ozanimod hydrochloride 3UPR33JAAM 1618636-37-5 HAOOCAKHSFYDBU-BDQAORGHSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zeposia Capsule 0.92 mg Oral Bristol Myers Squibb Pharma Eeig 2020-12-23 Not applicable EU 
Zeposia Capsule 0.92 mg/1 Oral Celgene Corporation 2020-03-27 Not applicable US 
Zeposia Capsule 0.92 mg Oral Bristol Myers Squibb Pharma Eeig 2020-12-23 Not applicable EU Zeposia Capsule 0.92 mg Oral Bristol Myers Squibb 2020-11-12 Not applicable Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Zeposia Ozanimod (0.23 mg) + Ozanimod (0.46 mg) Capsule Oral Bristol Myers Squibb Pharma Eeig 2020-12-23 Not applicable EU Zeposia Ozanimod hydrochloride (0.23 mg) + Ozanimod hydrochloride (0.46 mg) Capsule Oral Bristol Myers Squibb 2020-11-12 Not applicable Canada ZEPOSIA Ozanimod (0.46 MG) + Ozanimod (0.23 MG) Capsule; Kit Oral Bristol Myers Squibb Pharma Eeig 2020-12-05 Not applicable Italy 
Zeposia Ozanimod hydrochloride (0.23 mg) + Ozanimod hydrochloride (0.46 mg) Capsule Oral Bristol Myers Squibb 2020-11-12 Not applicable Canada Zeposia Ozanimod (0.23 mg) + Ozanimod (0.46 mg) Capsule Oral Bristol Myers Squibb Pharma Eeig 2020-12-23 Not applicable EU
Categories
- ATC Codes
- L04AE02 — Ozanimod
- Drug Categories
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Immunologic Factors
- Immunomodulatory Agents
- Immunosuppressive Agents
- Indenes
- Oxazoles
- P-glycoprotein substrates
- Selective Immunosuppressants
- Sphingosine 1 Phosphate Receptor Modulators
- Sphingosine 1-phosphate Receptor Modulator
- Sphingosine-1-phosphate (S1P) receptor modulators
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenyloxadiazoles. These are polycyclic aromatic compounds containing a benzene ring linked to a 1,2,4-oxadiazole ring through a CC or CN bond.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Oxadiazoles
- Direct Parent
- Phenyloxadiazoles
- Alternative Parents
- Indanes / Phenoxy compounds / Phenol ethers / Benzonitriles / Aralkylamines / Alkyl aryl ethers / Heteroaromatic compounds / 1,2-aminoalcohols / Oxacyclic compounds / Nitriles show 5 more
- Substituents
- 1,2-aminoalcohol / Alcohol / Alkanolamine / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzonitrile show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Z80293URPV
- CAS number
- 1306760-87-1
- InChI Key
- XRVDGNKRPOAQTN-FQEVSTJZSA-N
- InChI
- 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
- IUPAC Name
- 5-{3-[(1S)-1-[(2-hydroxyethyl)amino]-2,3-dihydro-1H-inden-4-yl]-1,2,4-oxadiazol-5-yl}-2-(propan-2-yloxy)benzonitrile
- SMILES
- CC(C)OC1=C(C=C(C=C1)C1=NC(=NO1)C1=C2CC[C@H](NCCO)C2=CC=C1)C#N
References
- Synthesis Reference
Florian Uthoff, Jana Löwe, Christina Harms, Kai Donsbach, Harald Gröger. Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. April 2019. The Journal of Organic Chemistry. DOI: 10.1021/acs.joc.8b03290
- General References
- Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdova E, Cree BAC, Sheffield JK, Minton N, Raghupathi K, Huang V, Kappos L: Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019 Nov;18(11):1021-1033. doi: 10.1016/S1474-4422(19)30238-8. Epub 2019 Sep 3. [Article]
- Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA: Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator. J Clin Pharmacol. 2017 Aug;57(8):988-996. doi: 10.1002/jcph.887. Epub 2017 Apr 11. [Article]
- Tran JQ, Hartung JP, Tompkins CA, Frohna PA: Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator. Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10. [Article]
- Ghasemi N, Razavi S, Nikzad E: Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. Epub 2016 Dec 21. [Article]
- Fakhoury M, Negrulj R, Mooranian A, Al-Salami H: Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res. 2014 Jun 23;7:113-20. doi: 10.2147/JIR.S65979. eCollection 2014. [Article]
- Vetter M, Neurath MF: Emerging oral targeted therapies in inflammatory bowel diseases: opportunities and challenges. Therap Adv Gastroenterol. 2017 Oct;10(10):773-790. doi: 10.1177/1756283X17727388. Epub 2017 Sep 5. [Article]
- Chaudhry BZ, Cohen JA, Conway DS: Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis. Neurotherapeutics. 2017 Oct;14(4):859-873. doi: 10.1007/s13311-017-0565-4. [Article]
- Cohen JA, Comi G, Arnold DL, Bar-Or A, Selmaj KW, Steinman L, Havrdova EK, Cree BA, Montalban X, Hartung HP, Huang V, Frohna P, Skolnick BE, Kappos L: Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study. Mult Scler. 2019 Aug;25(9):1255-1262. doi: 10.1177/1352458518789884. Epub 2018 Jul 25. [Article]
- Celgene: Press releases archive [Link]
- AJMC: FDA approves Zeposia (Ozanimod) for patients with RMS [Link]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- BioSpace News Release: Bristol Myers Squibb Receives European Commission Approval of Zeposia (ozanimod) for use in Adults with Moderately to Severely Active Ulcerative Colitis [Link]
- Summary of Product Characteristics: Zeposia (ozanimod) oral capsules [Link]
- Health Canada Approved Drug Products: ZEPOSIA (ozanimod) Oral Capsules [Link]
- External Links
- PubChem Compound
- 52938427
- PubChem Substance
- 347828826
- ChemSpider
- 34979946
- BindingDB
- 50507186
- 2288236
- ChEMBL
- CHEMBL3707247
- ZINC
- ZINC000116109867
- PDBe Ligand
- JEU
- Wikipedia
- Ozanimod
- PDB Entries
- 7ew0
- FDA label
- Download (369 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Multiple Sclerosis 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Ulcerative Colitis 1 somestatus stop reason just information to hide Not Available Completed Not Available Healthy Volunteers (HV) 1 somestatus stop reason just information to hide Not Available Enrolling by Invitation Not Available Adherence, Medication / Multiple Sclerosis 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Not Available Ulcerative Colitis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 0.92 mg/1 Capsule Oral 0.92 mg Capsule; kit Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8481573 No 2013-07-09 2029-05-14 US US9382217 No 2016-07-05 2029-05-14 US US8796318 No 2014-08-05 2029-05-14 US US10239846 No 2019-03-26 2030-11-15 US US11680050 No 2018-09-30 2038-09-30 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 134-137 https://www.trc-canada.com/product-detail/?CatNum=O880000&__cf_chl_jschl_tk__=47418a3658c1bed2236975a78c4d009d9726aa64-1585324169-0-AVBdS0uIBZsziaubuiosHQ9SfMRbB8tzILtS_D8ROwXY3jfZIfe7nf68lYLXjCK3VPlPXWBy25ZsDzjuSRHMsq4i6AooTGfw__9JzT3wXrvVSSMU2EcrV7Mv40mnq3e2lIo4_w_bP6jZ3VXuonZ_xdQiH-fceyd07BbLIF4BZmVUCw323soeydBwwDrMkF8dmXn9dgJ2cvO1O9LQY8_gDfhGL3Es8UF5YZpSXPUJEPZZo2_oXA4uk-2QpHpCZeR5oZIdF_CMMX2z5--DAw52pjMVLVTwvoNQS0ux0IEnKEV-UYKTAUK2pG7eAUZl2Cjvrg boiling point (°C) 648.3±65.0 https://www.chemsrc.com/en/cas/1306760-87-1_828967.html logP 3.73 https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8709 pKa 14.73±0.10 https://www.chemicalbook.com/ChemicalProductProperty_EN_CB42716147.htm - Predicted Properties
Property Value Source Water Solubility 0.161 mg/mL ALOGPS logP 2.81 ALOGPS logP 3.96 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 15.6 Chemaxon pKa (Strongest Basic) 8.96 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 104.2 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 135.66 m3·mol-1 Chemaxon Polarizability 45.21 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-0009700000-bdc342ffe8062d9f9287 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-3006900000-bf3493a63bdf49c15697 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0gvk-0009100000-8bfa7507ca68d6aa8083 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0zfu-0019100000-ac4c8a20c56ca29be9a3 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0kuu-1329100000-0daa99421a74fcc461a2 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-057l-2109000000-9d508940832266e9dd13 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 196.34586 predictedDeepCCS 1.0 (2019) [M+H]+ 198.70387 predictedDeepCCS 1.0 (2019) [M+Na]+ 205.09543 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- S1PR1
- Uniprot ID
- P21453
- Uniprot Name
- Sphingosine 1-phosphate receptor 1
- Molecular Weight
- 42810.195 Da
References
- Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdova E, Cree BAC, Sheffield JK, Minton N, Raghupathi K, Huang V, Kappos L: Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019 Nov;18(11):1021-1033. doi: 10.1016/S1474-4422(19)30238-8. Epub 2019 Sep 3. [Article]
- Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA: Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator. J Clin Pharmacol. 2017 Aug;57(8):988-996. doi: 10.1002/jcph.887. Epub 2017 Apr 11. [Article]
- Tran JQ, Hartung JP, Tompkins CA, Frohna PA: Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator. Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By similarity). May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- S1PR5
- Uniprot ID
- Q9H228
- Uniprot Name
- Sphingosine 1-phosphate receptor 5
- Molecular Weight
- 41774.515 Da
References
- Cohen JA, Comi G, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdova E, Cree BAC, Sheffield JK, Minton N, Raghupathi K, Huang V, Kappos L: Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019 Nov;18(11):1021-1033. doi: 10.1016/S1474-4422(19)30238-8. Epub 2019 Sep 3. [Article]
- Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA: Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator. J Clin Pharmacol. 2017 Aug;57(8):988-996. doi: 10.1002/jcph.887. Epub 2017 Apr 11. [Article]
- Tran JQ, Hartung JP, Tompkins CA, Frohna PA: Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator. Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10. [Article]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the oxidation of medium and long chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length (PubMed:18035827, PubMed:18182499, PubMed:22633490, PubMed:25047030, PubMed:9133646, PubMed:9662422). Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid (PubMed:22633490)
- Specific Function
- 3-chloroallyl aldehyde dehydrogenase activity
- Gene Name
- ALDH3A2
- Uniprot ID
- P51648
- Uniprot Name
- Aldehyde dehydrogenase family 3 member A2
- Molecular Weight
- 54847.36 Da
References
- Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, Peach RJ, Gujrathi S, Frohna PA: Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Dev. 2018 Mar;7(3):263-276. doi: 10.1002/cpdd.383. Epub 2017 Aug 7. [Article]
- Rasche L, Paul F: Ozanimod for the treatment of relapsing remitting multiple sclerosis. Expert Opin Pharmacother. 2018 Dec;19(18):2073-2086. doi: 10.1080/14656566.2018.1540592. Epub 2018 Nov 8. [Article]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing ethanol (PubMed:8460164). Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage (PubMed:33355142). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADH-dependent reduction of S-nitrosoglutathione, thereby regulating protein S-nitrosylation (By similarity)
- Specific Function
- alcohol dehydrogenase (NAD+) activity, zinc-dependent
- Gene Name
- ADH5
- Uniprot ID
- P11766
- Uniprot Name
- Alcohol dehydrogenase class-3
- Molecular Weight
- 39723.945 Da
References
- Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, Peach RJ, Gujrathi S, Frohna PA: Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Dev. 2018 Mar;7(3):263-276. doi: 10.1002/cpdd.383. Epub 2017 Aug 7. [Article]
- Rasche L, Paul F: Ozanimod for the treatment of relapsing remitting multiple sclerosis. Expert Opin Pharmacother. 2018 Dec;19(18):2073-2086. doi: 10.1080/14656566.2018.1540592. Epub 2018 Nov 8. [Article]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates (PubMed:12222688, PubMed:7915226). Participates in the detoxification of a plethora of hydrazine and arylamine drugs, and is able to bioactivate several known carcinogens
- Specific Function
- arylamine N-acetyltransferase activity
- Gene Name
- NAT2
- Uniprot ID
- P11245
- Uniprot Name
- Arylamine N-acetyltransferase 2
- Molecular Weight
- 33570.245 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924). Preferentially degrades benzylamine and phenylethylamine (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924)
- Specific Function
- aliphatic amine oxidase activity
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699)
- Specific Function
- 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
- Gene Name
- AKR1C1
- Uniprot ID
- Q04828
- Uniprot Name
- Aldo-keto reductase family 1 member C1
- Molecular Weight
- 36788.02 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:15929998, PubMed:17034817, PubMed:17442338, PubMed:8573067). Also specifically able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699)
- Specific Function
- aldose reductase (NADPH) activity
- Gene Name
- AKR1C2
- Uniprot ID
- P52895
- Uniprot Name
- Aldo-keto reductase family 1 member C2
- Molecular Weight
- 36734.97 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924). Preferentially degrades benzylamine and phenylethylamine (PubMed:11049757, PubMed:11134050, PubMed:20493079, PubMed:8316221, PubMed:8665924)
- Specific Function
- aliphatic amine oxidase activity
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Weak substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, Peach RJ, Gujrathi S, Frohna PA: Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Dev. 2018 Mar;7(3):263-276. doi: 10.1002/cpdd.383. Epub 2017 Aug 7. [Article]
- FDA Approved Drug Products: Zeposia (ozanimod) oral capsules [Link]
Drug created at October 20, 2016 23:12 / Updated at June 01, 2023 18:05