U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C12H9F3N2O2
Molecular Weight 270.2077
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 of TERIFLUNOMIDE

SMILES

C/C(=C(\C#N)/C(=O)Nc1ccc(cc1)C(F)(F)F)/O

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

Description
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

Curator's Comment:: Has only limited penetration across the blood–brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q02127
Gene ID: 1723.0
Gene Symbol: DHODH
Target Organism: Homo sapiens (Human)
160.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AUBAGIO

Approved Use

Indicated for the treatment of patients with relapsing forms of multiple sclerosis.

Launch Date

1.34740797E12
Palliative
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

9.0538561E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.06 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
100 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
243 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
TERIFLUNOMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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: Page: p.923
unhealthy, 36
n = 250
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 36
Sex: M+F
Population Size: 250
Sources: Page: p.923
Disc. AE: ALT increased, Hepatic enzyme increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (3.6%)
Hepatic enzyme increased (0.4%)
Sources: Page: p.923
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: Page: p.8,9
unhealthy, 37
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37
Sex: M+F
Sources: Page: p.8,9
Disc. AE: ALT increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (2.6%)
Sources: Page: p.8,9
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: Page: p.2781
unhealthy, 37.8 ± 9.7
n = 43
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37.8 ± 9.7
Sex: M+F
Population Size: 43
Sources: Page: p.2781
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (4.7%)
AST increased (4.7%)
Neutropenia (4.7%)
Sources: Page: p.2781
672 mg single, oral
Overdose
Dose: 672 mg
Route: oral
Route: single
Dose: 672 mg
Sources:
unknown
Health Status: unknown
Sources:
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
Disc. AE: Hepatotoxicity, Liver injury...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity
Liver injury (severe)
Liver failure (grade 5)
Disorder fetal
Sources: Page: p.1
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: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.7
Disc. AE: Peripheral neuropathy...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (1.9%)
Sources: Page: p.7
AEs

AEs

AESignificanceDosePopulation
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: Page: p.923
unhealthy, 36
n = 250
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 36
Sex: M+F
Population Size: 250
Sources: Page: p.923
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: Page: p.923
unhealthy, 36
n = 250
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 36
Sex: M+F
Population Size: 250
Sources: Page: p.923
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: Page: p.8,9
unhealthy, 37
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37
Sex: M+F
Sources: Page: p.8,9
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: Page: p.2781
unhealthy, 37.8 ± 9.7
n = 43
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37.8 ± 9.7
Sex: M+F
Population Size: 43
Sources: Page: p.2781
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: Page: p.2781
unhealthy, 37.8 ± 9.7
n = 43
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37.8 ± 9.7
Sex: M+F
Population Size: 43
Sources: Page: p.2781
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: Page: p.2781
unhealthy, 37.8 ± 9.7
n = 43
Health Status: unhealthy
Condition: Multiple sclerosis
Age Group: 37.8 ± 9.7
Sex: M+F
Population Size: 43
Sources: Page: p.2781
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.1
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: Page: p.7
unhealthy
Health Status: unhealthy
Condition: Multiple sclerosis
Sources: Page: p.7
PubMed

PubMed

TitleDatePubMed
Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria.
1998 Oct 15
Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression.
1999 Feb 15
Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis.
1999 Nov
The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review.
2000 May
Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases.
2000 May
Immunosuppressive drugs: the first 50 years and a glance forward.
2000 May
Serious liver disease in a patient receiving methotrexate and leflunomide.
2000 Nov
Leflunomide: mode of action in the treatment of rheumatoid arthritis.
2000 Nov
Vasculitis occurring during leflunomide therapy.
2001
The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis.
2001
Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.
2001
Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine A, mycophenolate mofetil, and leflunomide remain normoglycemic for up to 100 days.
2001 Apr 27
Novel therapies in the treatment of systemic lupus erythematosus.
2001 Aug
Leflunomide Aventis Pharma.
2001 Feb
Radiography of rheumatoid arthritis in the time of increasing drug effectiveness.
2001 Feb
Newer immunomodulating drugs in rheumatoid arthritis may precipitate glomerulonephritis.
2001 Jan
Leflunomide inhibits activation of inducible nitric oxide synthase in rat astrocytes.
2001 Jan 19
Treatment of immune-mediated skin diseases: future perspectives.
2001 Jul-Aug
Conventional DMARD options for patients with a suboptimal response to methotrexate.
2001 Jun
Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.
2001 Mar
Inhibition of cyclosporin-resistant B-cell antigen responses by pyrazoles: a tool for the identification of novel molecular mechanisms of B-cell activation.
2001 May
Which HAQ is best? A comparison of the HAQ, MHAQ and RA-HAQ, a difficult 8 item HAQ (DHAQ), and a rescored 20 item HAQ (HAQ20): analyses in 2,491 rheumatoid arthritis patients following leflunomide initiation.
2001 May
[Leflunomide--a new disease modifying anti-rheumatic agent].
2001 Nov 10
Inhibition of angiogenesis-related endothelial activity by the experimental immunosuppressive agent leflunomide.
2001 Nov 15
Augmentation of apoptosis responses in p53-deficient L1210 cells by compounds directed at blocking NFkappaB activation.
2001 Nov-Dec
Current and emerging lupus treatments.
2001 Oct
Inhibition of HIV replication by A77 1726, the active metabolite of leflunomide, in combination with pyrimidine nucleoside reverse transcriptase inhibitors.
2001 Oct 1
Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study.
2001 Sep
Treating rheumatoid arthritis with new disease modifying drugs.
2002
Treatment of severe psoriasis and psoriatic arthritis with leflunomide.
2002 Feb
Experiences with leflunomide in solid organ transplantation.
2002 Feb 15
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

20 mg once daily
Route of Administration: Oral
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.
Name Type Language
TERIFLUNOMIDE
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
LEFLUNOMIDE SPECIFIED IMPURITY B [EP]
Common Name English
LEFLUNOMIDE RELATED COMPOUND B [USP]
Common Name English
TERIFLUNOMIDE [MI]
Common Name English
TERIFLUNOMIDE [INN]
Common Name English
AUBAGIO
Brand Name English
HMR-1726
Code English
LEFLUNOMIDE RELATED COMPOUND B
USP  
Common Name English
TERIFLUNOMIDE [USAN]
Common Name English
HMR1726
Code English
TERIFLUNOMIDE [WHO-DD]
Common Name English
LEFLUNOMIDE RELATED COMPOUND B RS [USP]
Common Name English
2-BUTENAMIDE, 2-CYANO-3-HYDROXY-N-(4-(TRIFLUOROMETHYL)PHENYL)-, (2Z)-
Systematic Name English
TERIFLUNOMIDE [ORANGE BOOK]
Common Name English
A77 1726
Code English
TERIFLUNOMIDE [VANDF]
Common Name English
TERIFLUNOMIDE [EP MONOGRAPH]
Common Name English
LEFLUNOMIDE RELATED COMPOUND B [USP-RS]
Common Name English
Classification Tree Code System Code
LIVERTOX 940
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
WHO-VATC QL04AA31
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
NCI_THESAURUS C471
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
EMA ASSESSMENT REPORTS AUBAGIO (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
NDF-RT N0000185502
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
WHO-ATC L04AA31
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
Code System Code Type Description
DRUG BANK
DB08880
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
PUBCHEM
54684141
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
EVMPD
SUB25218
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
MESH
C527525
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
WIKIPEDIA
TERIFLUNOMIDE
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
FDA UNII
1C058IKG3B
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
LACTMED
Teriflunomide
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
INN
7761
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
NDF-RT
N0000185501
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY Dihydroorotate Dehydrogenase Inhibitors [MoA]
MERCK INDEX
M10578
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL973
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
CAS
108605-62-5
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
NCI_THESAURUS
C76662
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
USP_CATALOG
1357056
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
4634
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
IUPHAR
6844
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY
RXCUI
1310520
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY RxNorm
CAS
163451-81-8
Created by admin on Fri Jun 25 21:06:28 UTC 2021 , Edited by admin on Fri Jun 25 21:06:28 UTC 2021
PRIMARY