Teriflunomide

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H9F3N2O2
Molecular Weight	270.2073
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0
Stereo Comments	Teriflunomide then can interconvert between the E and Z enolic forms (and the corresponding keto-amide), with the Z-enol being the most stable and therefore most predominant form (https://en.wikipedia.org/wiki/Leflunomide)

SHOW SMILES / InChI

Structure Search

SMILES

C\C(O)=C(/C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F

InChI

InChIKey=UTNUDOFZCWSZMS-YFHOEESVSA-N

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-

HIDE SMILES / InChI

Molecular Formula	C12H9F3N2O2
Molecular Weight	270.2073
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020905s031lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202992s003lbl.pdf
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00622700?term=teriflunomide&rank=8

Teriflunomide (trade name Aubagio, marketed by Sanofi) is the active metabolite of leflunomide and it acts as an immunomodulatory agent by inhibiting pyrimidine synthesis by blocking the enzyme dihydroorotate dehydrogenase. Teriflunomide was investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). The drug was approved by the FDA on September 13, 2012 and in the European Union on August 26, 2013. It is uncertain whether this explains its effect on MS lesions. Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Teriflunomide may decrease the risk of infections compared to chemotherapy-like drugs because of its more-limited effects on the immune system. It has been found that teriflunomide blocks the transcription factor NF-κB. It also inhibits tyrosine kinase enzymes, but only in high doses not clinically used.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydroorotate dehydrogenase (quinone), mitochondrial 3 Target ID: Q02127 Gene ID: 1723.0 Gene Symbol: DHODH Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202992s003lbl.pdf	Inhibitor 8504		160.0 nM [Ki]
Dihydroorotate dehydrogenase 10 Target ID: CHEMBL1966 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9666414	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple sclerosis 107 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202992s003lbl.pdf	Primary		Approved 8583	AUBAGIO Approved Use Indicated for the treatment of patients with relapsing forms of multiple sclerosis. Launch Date 2012
Active rheumatoid arthritis 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020905s031lbl.pdf	Palliative		Approved 8583	ARAVA Approved Use Leflunomide is indicated in adults for the treatment of active rheumatoid arthritis (RA): to reduce signs and symptoms to inhibit structural damage as evidenced by X-ray erosions and joint space narrowing to improve physical function (see CLINICAL STUDIES ). Aspirin, nonsteroidal anti-inflammatory agents and/or low dose corticosteroids may be continued during treatment with leflunomide (see PRECAUTIONS: Drug Interactions: NSAIDs ). The combined use of leflunomide with antimalarials, intramuscular or oral gold, D penicillamine, azathioprine, or methotrexate has not been adequately studied (see WARNINGS: Immunosuppression Potential/Bone Marrow Suppression ). Launch Date 1998

C_max

Value	Dose	Co-administered	Analyte	Population
1.06 μg/mL EXPERIMENT https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202992Orig1s000ClinpharmR.pdf	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:		TERIFLUNOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
100 μg × h/mL EXPERIMENT https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202992Orig1s000ClinpharmR.pdf	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:		TERIFLUNOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
243 h EXPERIMENT https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202992Orig1s000ClinpharmR.pdf	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:		TERIFLUNOMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202992s000lbl.pdf			TERIFLUNOMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26865517	unhealthy, 36 Health Status: unhealthy Age Group: 36 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/26865517	Disc. AE: ALT increased, Hepatic enzyme increased... AEs leading to discontinuation/dose reduction: ALT increased (3.6%) Hepatic enzyme increased (0.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/26865517
14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy, 37 Health Status: unhealthy Age Group: 37 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	Disc. AE: ALT increased... AEs leading to discontinuation/dose reduction: ALT increased (2.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30511679	unhealthy, 37.8 ± 9.7 Health Status: unhealthy Age Group: 37.8 ± 9.7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/30511679	Disc. AE: ALT increased, AST increased... AEs leading to discontinuation/dose reduction: ALT increased (4.7%) AST increased (4.7%) Neutropenia (4.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/30511679
672 mg single, oral Overdose Dose: 672 mg Route: oral Route: single Dose: 672 mg Sources: https://pubmed.ncbi.nlm.nih.gov/33421160	unknown Health Status: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/33421160	Sources: https://pubmed.ncbi.nlm.nih.gov/33421160
14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	Disc. AE: Hepatotoxicity, Liver injury... AEs leading to discontinuation/dose reduction: Hepatotoxicity Liver injury (severe) Liver failure (grade 5) Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	Disc. AE: Peripheral neuropathy... AEs leading to discontinuation/dose reduction: Peripheral neuropathy (1.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf

AEs

AE	Significance	Dose	Population
Hepatic enzyme increased	0.4% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26865517	unhealthy, 36 Health Status: unhealthy Age Group: 36 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/26865517
ALT increased	3.6% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26865517	unhealthy, 36 Health Status: unhealthy Age Group: 36 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/26865517
ALT increased	2.6% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy, 37 Health Status: unhealthy Age Group: 37 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
ALT increased	4.7% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30511679	unhealthy, 37.8 ± 9.7 Health Status: unhealthy Age Group: 37.8 ± 9.7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/30511679
AST increased	4.7% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30511679	unhealthy, 37.8 ± 9.7 Health Status: unhealthy Age Group: 37.8 ± 9.7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/30511679
Neutropenia	4.7% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30511679	unhealthy, 37.8 ± 9.7 Health Status: unhealthy Age Group: 37.8 ± 9.7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/30511679
Disorder fetal	Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
Hepatotoxicity	Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
Liver failure	grade 5 Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
Liver injury	severe Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf
Peripheral neuropathy	1.9% Disc. AE	14 mg 1 times / day multiple, oral Recommended Dose: 14 mg, 1 times / day Route: oral Route: multiple Dose: 14 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202992s006lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68540	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68540
ChemicalBook	CB02486749	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02486749
ChemicalBook	CB5648113	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5648113
ChemicalBook	CB6464433	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6464433
eMolecules	26948188	https://www.emolecules.com/cgi-bin/more?vid=26948188
MolPort	MolPort-005-943-824	https://www.molport.com/shop/molecule-link/MolPort-005-943-824
ZINC	ZINC000013512456	http://zinc15.docking.org/substances/ZINC000013512456

PubMed

Title	Date	PubMed
Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide.	1998 May 1	10076546
Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria.	1998 Oct 15	9776318
Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis.	1999 Nov	10890256
The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review.	2000 May	10878295
Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases.	2000 May	10878294
Leflunomide: mode of action in the treatment of rheumatoid arthritis.	2000 Nov	11053058
The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis.	2001	11686882
A clinical and economic review of disease-modifying antirheumatic drugs.	2001	11548909
Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine.	2001	11469522
Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.	2001	11438040
A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer.	2001 Apr	11309325
The Saccharomyces cerevisiae MLF6/YPL244C gene, which encodes a possible yeast homologue of mammalian UDP-galactose transporter, confers resistance to the immunosuppressive drug, leflunomide.	2001 Aug	11391470
[Evidence-based medicine and applying new therapies in general practice: wish and reality].	2001 Dec	11826740
Acetyl-coa: alcohol acetyltransferase activity and aroma formation in ripening melon fruits.	2001 Feb	11262031
Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child.	2001 Feb	11241434
Combination of antilymphocyte globulin and leflunomide leads to superior grafts.	2001 Feb-Mar	11266962
Flow cytometric quantitation of calcium-dependent and -independent mitogen-stimulation of T cell functions in whole blood: inhibition by immunosuppressive drugs in vitro.	2001 Jul 1	11384672
Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis.	2001 Jul-Aug	11491512
Treatment of immune-mediated skin diseases: future perspectives.	2001 Jul-Aug	11399542
Treating early rheumatoid arthritis in the younger patient.	2001 Jun	11409156
Conventional DMARD options for patients with a suboptimal response to methotrexate.	2001 Jun	11409154
Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.	2001 Mar	11224696
Comorbidity in rheumatoid arthritis.	2001 May	11396093
Leflunomide-associated weight loss in rheumatoid arthritis.	2001 May	11352235
[Chronic polyarthritis].	2001 May 24	11420837
[Leflunomide--a new disease modifying anti-rheumatic agent].	2001 Nov 10	11876141
Severe liver damage with leflunomide.	2001 Oct	11824431
Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine.	2001 Oct	11557646
Is there a place for leflunomide in the treatment of rheumatoid arthritis?	2001 Oct 13	11675052
Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study.	2001 Sep	11568668
Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: an evaluation based on a 1-year randomised controlled trial.	2002	11817993
Experiences with leflunomide in solid organ transplantation.	2002 Feb 15	11884931
Leflunomide induced fevers, thrombocytosis, and leukocytosis in a patient with relapsing polychondritis.	2002 Jan	11824960
Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase.	2007 Jan 25	17228860
Hepatic cytochrome P450s attenuate the cytotoxicity induced by leflunomide and its active metabolite A77 1726 in primary cultured rat hepatocytes.	2011 Aug	21546349
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

20 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Cell cultures were inoculated with feline herpesvirus-1 (FHV-1) and treated simultaneously with concentrations of A77 (active metabolite of leflunomide, A77 1726) ranging from 0 to 200 uM. Concentrations of A77 > or = 20 uM were associated with substantial reduction in plaque number and viral load. Concentrations > or = 100 uM were associated with complete suppression of plaque formation. At low concentrations of A77, clusters of intracytoplasmic virus particles that appeared to lack tegument and an external membrane were detected.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:06:42 GMT 2025` Edited by `admin` on `Mon Mar 31 18:06:42 GMT 2025`
Record UNII	1C058IKG3B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEFLUNOMIDE RELATED COMPOUND B

Preferred Name

English

Teriflunomide

Official Name

English

TERIFLUNOMIDE [MI]

Common Name

English

teriflunomide [INN]

Common Name

English

AUBAGIO

Brand Name

English

HMR-1726

Code

English

TERIFLUNOMIDE [USAN]

Common Name

English

HMR1726

Code

English

LEFLUNOMIDE RELATED COMPOUND B [USP IMPURITY]

Common Name

English

2-BUTENAMIDE, 2-CYANO-3-HYDROXY-N-(4-(TRIFLUOROMETHYL)PHENYL)-, (2Z)-

Systematic Name

English

LEFLUNOMIDE IMPURITY B [EP IMPURITY]

Common Name

English

TERIFLUNOMIDE [ORANGE BOOK]

Common Name

English

A77 1726

Code

English

TERIFLUNOMIDE [VANDF]

Common Name

English

Teriflunomide [WHO-DD]

Common Name

English

TERIFLUNOMIDE [EP MONOGRAPH]

Common Name

English

LEFLUNOMIDE RELATED COMPOUND B [USP-RS]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548525