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This repository is under review for potential modification in compliance with Administration directives.

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 of Teriflunomide

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
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

2012
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

1998
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:
unhealthy, 36
Health Status: unhealthy
Age Group: 36
Sex: M+F
Sources:
Disc. AE: ALT increased, Hepatic enzyme increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (3.6%)
Hepatic enzyme increased (0.4%)
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:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
Disc. AE: ALT increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (2.6%)
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:
unhealthy, 37.8 ± 9.7
Health Status: unhealthy
Age Group: 37.8 ± 9.7
Sex: M+F
Sources:
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (4.7%)
AST increased (4.7%)
Neutropenia (4.7%)
Sources:
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:
unhealthy
Disc. AE: Hepatotoxicity, Liver injury...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity
Liver injury (severe)
Liver failure (grade 5)
Disorder fetal
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:
unhealthy
Disc. AE: Peripheral neuropathy...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (1.9%)
Sources:
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:
unhealthy, 36
Health Status: unhealthy
Age Group: 36
Sex: M+F
Sources:
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:
unhealthy, 36
Health Status: unhealthy
Age Group: 36
Sex: M+F
Sources:
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:
unhealthy, 37
Health Status: unhealthy
Age Group: 37
Sex: M+F
Sources:
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:
unhealthy, 37.8 ± 9.7
Health Status: unhealthy
Age Group: 37.8 ± 9.7
Sex: M+F
Sources:
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:
unhealthy, 37.8 ± 9.7
Health Status: unhealthy
Age Group: 37.8 ± 9.7
Sex: M+F
Sources:
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:
unhealthy, 37.8 ± 9.7
Health Status: unhealthy
Age Group: 37.8 ± 9.7
Sex: M+F
Sources:
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
PubMed

PubMed

TitleDatePubMed
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
Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria.
1998 Oct 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
Leflunomide: mode of action in the treatment of rheumatoid arthritis.
2000 Nov
The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis.
2001
A clinical and economic review of disease-modifying antirheumatic drugs.
2001
Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine.
2001
Bone loss. Therapeutic approaches for preventing bone loss in inflammatory arthritis.
2001
A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer.
2001 Apr
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
[Evidence-based medicine and applying new therapies in general practice: wish and reality].
2001 Dec
Acetyl-coa: alcohol acetyltransferase activity and aroma formation in ripening melon fruits.
2001 Feb
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
Combination of antilymphocyte globulin and leflunomide leads to superior grafts.
2001 Feb-Mar
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
Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis.
2001 Jul-Aug
Treatment of immune-mediated skin diseases: future perspectives.
2001 Jul-Aug
Treating early rheumatoid arthritis in the younger patient.
2001 Jun
Conventional DMARD options for patients with a suboptimal response to methotrexate.
2001 Jun
Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.
2001 Mar
Comorbidity in rheumatoid arthritis.
2001 May
Leflunomide-associated weight loss in rheumatoid arthritis.
2001 May
[Chronic polyarthritis].
2001 May 24
[Leflunomide--a new disease modifying anti-rheumatic agent].
2001 Nov 10
Severe liver damage with leflunomide.
2001 Oct
Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine.
2001 Oct
Is there a place for leflunomide in the treatment of rheumatoid arthritis?
2001 Oct 13
Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study.
2001 Sep
Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: an evaluation based on a 1-year randomised controlled trial.
2002
Experiences with leflunomide in solid organ transplantation.
2002 Feb 15
Leflunomide induced fevers, thrombocytosis, and leukocytosis in a patient with relapsing polychondritis.
2002 Jan
Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase.
2007 Jan 25
Hepatic cytochrome P450s attenuate the cytotoxicity induced by leflunomide and its active metabolite A77 1726 in primary cultured rat hepatocytes.
2011 Aug
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.
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
  • Download
Name Type Language
LEFLUNOMIDE RELATED COMPOUND B
USP  
Preferred Name English
Teriflunomide
DASH   INN   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
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
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
WHO-VATC QL04AA31
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
NCI_THESAURUS C471
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
EMA ASSESSMENT REPORTS AUBAGIO (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
NDF-RT N0000185502
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
WHO-ATC L04AA31
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
Code System Code Type Description
DRUG BANK
DB08880
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
CHEBI
68540
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
PUBCHEM
54684141
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
EVMPD
SUB25218
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
RS_ITEM_NUM
1357056
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
MESH
C527525
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
WIKIPEDIA
TERIFLUNOMIDE
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
USAN
YY-88
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
FDA UNII
1C058IKG3B
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
LACTMED
Teriflunomide
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
INN
7761
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
SMS_ID
100000089234
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
NDF-RT
N0000185501
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY Dihydroorotate Dehydrogenase Inhibitors [MoA]
EPA CompTox
DTXSID80893457
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
MERCK INDEX
m10578
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL973
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
CAS
108605-62-5
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
NON-SPECIFIC STEREOCHEMISTRY
NCI_THESAURUS
C76662
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
DAILYMED
1C058IKG3B
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
DRUG CENTRAL
4634
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
IUPHAR
6844
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
RXCUI
1310520
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY RxNorm
CAS
163451-81-8
Created by admin on Mon Mar 31 18:06:42 GMT 2025 , Edited by admin on Mon Mar 31 18:06:42 GMT 2025
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
EXCRETED UNCHANGED
FECAL
TRANSPORTER -> INHIBITOR
Terifluniomide is an inhibitor of BCRP, OAT3, OATP1B1, OCT2 in vitro
TRANSPORTER -> INHIBITOR
Terifluniomide is an inhibitor of BCRP, OAT3, OATP1B1, OCT2 in vitro
EXCRETED UNCHANGED
URINE
TRANSPORTER -> INHIBITOR
Terifluniomide is an inhibitor of BCRP, OAT3, OATP1B1, OCT2 in vitro
TARGET -> INHIBITOR
INHIBITOR
IC50
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
TRANSPORTER -> INHIBITOR
Terifluniomide is an inhibitor of BCRP, OAT3, OATP1B1, OCT2 in vitro
TRANSPORTER -> SUBSTRATE
Teriflunomide is a substrate of BCRP in vitro
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
4-TFMA was not detected in the single dose metabolism study, but was detected in very small amount after repeated dosing in clinical trials 4-TFMA plasma concentrations were measurable at relatively low concentrations after repeated teriflunomide doses of 7 mg (?1.7 ng/mL) and 14 mg (?5.31 ng/mL) for 468 weeks.
MINOR
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
PARENT -> IMPURITY
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC DOSE

Tmax PHARMACOKINETIC ORAL ADMINISTRATION