Identification
- Summary
Teriflunomide is a pyrimidine synthesis inhibitor with anti-inflammatory and immunomodulatory properties used to treat patients with the relapsing-remitting form of multiple sclerosis.
- Brand Names
- Aubagio
- Generic Name
- Teriflunomide
- DrugBank Accession Number
- DB08880
- Background
Teriflunomide is the active metabolite of leflunomide, and it acts as an immunomodulatory agent by inhibiting pyrimidine synthesis. It is marketed under the name Aubagio® and is indicated for the treatment of multiple sclerosis, specifically relapsing forms. The FDA label states an important warning about the risk of hepatoxicity and teratogenicity for patients using teriflunomide.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Teriflunomide (DB08880)
- Weight
- Average: 270.2073
Monoisotopic: 270.061612157 - Chemical Formula
- C12H9F3N2O2
- Synonyms
- (Z)-2-cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-p-crotonotoluidide
- Teriflunomida
- Tériflunomide
- Teriflunomide
- Teriflunomidum
- External IDs
- A 77-1726
- A 771726
- A-771726
- A77 1726
- A771726
- HMR 1726
- HMR-1726
- HMR1726
Pharmacology
- Indication
Used in the treatment of relapsing forms of multiple sclerosis (MS).
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 Management 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
Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.
- Mechanism of action
The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.
Target Actions Organism UDihydroorotate dehydrogenase (quinone), mitochondrial inhibitorHumans - Absorption
After oral administration of teriflunomide, maximum plasma concentrations are reached, on average, in 1-4 hours.
- Volume of distribution
After a single intravenous dose, the volume of distribution is 11 L.
- Protein binding
Teriflunomide is extensively plasma protein bound(>99%).
- Metabolism
Teriflunomide mainly undergoes hydrolyis to minor metabolites. Other minor metabolic pathways include oxidation, N-acetylation and sulfate conjugation. Teriflunomide is not metabolized by CYP450 or flavin monoamine oxidase.
- Route of elimination
Teriflunomide is eliminated unchanged and mainly through bile. Specifically 37.5% is eliminated in the feces and 22.6% in urine.
- Half-life
The median half-life is 18 to 19 days.
- Clearance
After a single IV dose, teriflunomide has a total body clearance of 30.5 mL/h.
- 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
Teriflunomide is contraindicated in pregnant women or women of childbearing age due to the risk of teratogenicity. Teriflunomide is also contraindicated in severe hepatic impairment due to reports of hepatotoxicity, hepatic failure, and death.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Teriflunomide. Abemaciclib Teriflunomide may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Acamprosate The excretion of Acamprosate can be decreased when combined with Teriflunomide. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Teriflunomide. Acetaminophen The serum concentration of Acetaminophen can be decreased when it is combined with Teriflunomide. - Food Interactions
- 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aubagio Tablet, film coated 14 mg/1 Oral Genzyme Corporation 2013-05-01 Not applicable US 
Aubagio Tablet, film coated 7 mg Oral SANOFI WINTHROP INDUSTRIE 2022-05-04 Not applicable EU 
Aubagio Tablet, film coated 14 mg Oral SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU Aubagio Tablet, film coated 7 mg/1 Oral Genzyme Corporation 2013-05-01 Not applicable US Aubagio Tablet, film coated 14 mg Oral SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-teriflunomide Tablet 14 mg Oral Accord Healthcare Inc 2022-05-19 Not applicable Canada 
Apo-teriflunomide Tablet 14 mg Oral Apotex Corporation 2022-05-16 Not applicable Canada Auro-teriflunomide Tablet 14 mg Oral Auro Pharma Inc Not applicable Not applicable Canada Jamp Teriflunomide Tablet 14 mg Oral Jamp Pharma Corporation 2022-05-16 Not applicable Canada Mar-teriflunomide Tablet 14 mg Oral Marcan Pharmaceuticals Inc 2022-05-18 Not applicable Canada
Categories
- ATC Codes
- L04AA31 — Teriflunomide
- Drug Categories
- Acids, Acyclic
- Amines
- Analgesics
- Analgesics, Non-Narcotic
- Aniline Compounds
- Anti-Inflammatory Agents
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Benzene Derivatives
- Butyrates
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 CYP1A2 Inducers (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Dihydroorotate Dehydrogenase Inhibitors
- Fatty Acids
- Fatty Acids, Volatile
- Hepatotoxic Agents
- Hydroxy Acids
- Immunologic Factors
- Immunomodulatory Agents
- Immunosuppressive Agents
- Lipids
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- Peripheral Nervous System Agents
- Pyrimidine Synthesis Inhibitor
- Selective Immunosuppressants
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Trifluoromethylbenzenes
- Direct Parent
- Trifluoromethylbenzenes
- Alternative Parents
- Anilides / N-arylamides / Vinylogous acids / Secondary carboxylic acid amides / Nitriles / Enols / Organopnictogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives show 2 more
- Substituents
- Alkyl fluoride / Alkyl halide / Anilide / Aromatic homomonocyclic compound / Carbonitrile / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Enol / Hydrocarbon derivative show 13 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- nitrile, enamide, aromatic amide, enol, (trifluoromethyl)benzenes (CHEBI:68540)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1C058IKG3B
- CAS number
- 163451-81-8
- InChI Key
- UTNUDOFZCWSZMS-YFHOEESVSA-N
- InChI
- InChI=1S/C12H9F3N2O2/c1-7(18)10(6-16)11(19)17-9-4-2-8(3-5-9)12(13,14)15/h2-5,18H,1H3,(H,17,19)/b10-7-
- IUPAC Name
- (2Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide
- SMILES
- C\C(O)=C(/C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F
References
- Synthesis Reference
Keshav Deo, Samir Patel, Snehal Dhol, Sunil Sanghani, Vishal Ray, " PROCESS FOR PREPARING TERIFLUNOMIDE." U.S. Patent US20110092727, issued April 21, 2011.
US20110092727- General References
- O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R: A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006 Mar 28;66(6):894-900. [Article]
- Tallantyre E, Evangelou N, Constantinescu CS: Spotlight on teriflunomide. Int MS J. 2008 Jun;15(2):62-8. [Article]
- FDA Approved Drug Products: AUBAGIO (teriflunomide) tablets [Link]
- External Links
- KEGG Drug
- D10172
- PubChem Compound
- 54684141
- PubChem Substance
- 347827807
- ChemSpider
- 16737143
- BindingDB
- 50018011
- 1310520
- ChEBI
- 68540
- ChEMBL
- CHEMBL973
- ZINC
- ZINC000013512456
- PDBe Ligand
- A26
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Teriflunomide
- PDB Entries
- 1d3h / 1tv5
- FDA label
- Download (527 KB)
- MSDS
- Download (124 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Multiple Sclerosis 3 4 Completed Treatment Multiple Sclerosis, Pharmacokinetics 1 4 Completed Treatment Relapsing Multiple Sclerosis (RMS) 1 4 Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 3 Active Not Recruiting Treatment Multiple Sclerosis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 14 mg Tablet Oral 14.000 mg Tablet, film coated Oral 7 MG Tablet, film coated Oral 14 mg Tablet, film coated Oral 14.0 mg Tablet Oral 14 mg/1 Tablet Oral 7 mg/1 Tablet, coated Oral 14 mg/1 Tablet, coated Oral 7 mg/1 Tablet, film coated Oral 14 mg/1 Tablet, film coated Oral 7 mg/1 Tablet, coated Oral 14 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6794410 Yes 2004-09-21 2027-03-12 US US9186346 Yes 2015-11-17 2034-08-04 US US8802735 Yes 2014-08-12 2031-03-14 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Soluble in DMSO (practically insoluble in water). From FDA label. - Predicted Properties
Property Value Source Water Solubility 0.0124 mg/mL ALOGPS logP 2.3 ALOGPS logP 2.14 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 5.48 Chemaxon pKa (Strongest Basic) -3.2 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 73.12 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 64.39 m3·mol-1 Chemaxon Polarizability 23.15 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0gvo-7890000000-a02cc8999b41f93431c0 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9100000000-2a60cc190de61052600c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-5090000000-234a7b4755738cefe042 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9000000000-96b31ed1fcc72ae700a5 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-1900000000-f0a06b6314701f5201f4 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00kf-9210000000-0f3745960114418f4083 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-5900000000-c6f7e506c6a2813d650c 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]- 158.53004 predictedDeepCCS 1.0 (2019) [M+H]+ 160.88805 predictedDeepCCS 1.0 (2019) [M+Na]+ 167.66957 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Ubiquinone binding
- Specific Function
- Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
- Gene Name
- DHODH
- Uniprot ID
- Q02127
- Uniprot Name
- Dihydroorotate dehydrogenase (quinone), mitochondrial
- Molecular Weight
- 42866.93 Da
References
- Palmer AM: Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis. Curr Opin Investig Drugs. 2010 Nov;11(11):1313-23. [Article]
- Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA: The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry. 1996 Jan 30;35(4):1270-3. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Kis E, Nagy T, Jani M, Molnar E, Janossy J, Ujhellyi O, Nemet K, Heredi-Szabo K, Krajcsi P: Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis. 2009 Jul;68(7):1201-7. doi: 10.1136/ard.2007.086264. Epub 2008 Apr 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
Drug created at May 20, 2013 02:55 / Updated at February 20, 2024 23:55