Teriflunomide

Summary

Teriflunomide (CHEMBL973) is an approved small-molecule EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor (ATC L04AK02) targeting DHODH; indicated across 7 conditions including multiple sclerosis and relapsing-remitting multiple sclerosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AK02
• Targets: 1 (DHODH)
• Indications: 7 conditions
• Clinical trials: 56
• Chemistry: C12H9F3N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL973
Name	Teriflunomide
Type	Small molecule
Max phase	4
ChEBI	CHEBI:68540
ATC	L04AK02
Molecular formula	C12H9F3N2O2
InChIKey	UTNUDOFZCWSZMS-YFHOEESVSA-N

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

ChEBI definition: An enamide obtained by formal condensation of the carboxy group of (2Z)-2-cyano-3-hydroxybut-2-enoic acid with the anilino group of 4-(trifluoromethyl)aniline. Used for the treatment of relapsing forms of multiple sclerosis and rheumatoid arthritis.

Pharmacological roles (ChEBI): EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor, tyrosine kinase inhibitor, hepatotoxic agent, non-steroidal anti-inflammatory drug.

Other ChEBI roles (chemical / environmental): drug metabolite.

Also known as: A77 1726, Aubagio, HMR-1726, HMR1726, Leflunomide related compound b, Leflunomide related compound b rs, Teriflunomida, Teriflunomide, Teriflunomide accord, Teriflunomide mylan, TERIFLUNOMIDE, teriflunomide

Patent coverage: 2,009 distinct patent families (7,575 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DHODH	dihydroorotate dehydrogenase (quinone)	Inhibition	6.51	33.9%	Q02127

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Amine oxidase [flavin-containing] A, Dihydroorotate dehydrogenase (quinone), mitochondrial, Dihydrofolate reductase, 5-hydroxytryptamine receptor 2A, Alpha-1A adrenergic receptor, Peroxisome proliferator-activated receptor gamma, Dihydroorotate dehydrogenase (quinone), mitochondrial, Dihydroorotate dehydrogenase (quinone), mitochondrial, ORAI1/STIM1.

Bioactivity

ChEMBL activities: 39 potent at pChembl ≥ 5 of 42 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q63707	8.05	IC50	9	nM	CHEMBL_ACT_1602499
Q63707	7.89	IC50	13	nM	CHEMBL_ACT_58279
Q63707	7.77	IC50	17	nM	CHEMBL_ACT_20608007
Q63707	7.75	IC50	18	nM	CHEMBL_ACT_14734090
Q63707	7.7	IC50	20	nM	CHEMBL_ACT_5177294
Q63707	7.7	IC50	20	nM	CHEMBL_ACT_8014133
Q63707	7.58	IC50	26	nM	CHEMBL_ACT_7971622
DHODH	7.52	Ki	30	nM	CHEMBL_ACT_1804327
DHODH	7.5	Ki	32	nM	CHEMBL_ACT_2525699
O35435	7.16	IC50	69	nM	CHEMBL_ACT_58278
O35435	6.96	IC50	110	nM	CHEMBL_ACT_20608006
DHODH	6.89	IC50	130	nM	CHEMBL_ACT_12137839
DHODH	6.86	IC50	137	nM	CHEMBL_ACT_13464377
O35435	6.82	IC50	150	nM	CHEMBL_ACT_14734101
O35435	6.81	IC50	156	nM	CHEMBL_ACT_1602500
DHODH	6.79	IC50	163	nM	CHEMBL_ACT_15201222
DHODH	6.68	IC50	210	nM	CHEMBL_ACT_14734104
DHODH	6.64	IC50	227	nM	CHEMBL_ACT_24402218
DHODH	6.58	IC50	260	nM	CHEMBL_ACT_1801667
DHODH	6.58	IC50	261	nM	CHEMBL_ACT_2525735
DHODH	6.52	IC50	300	nM	CHEMBL_ACT_20608005
DHODH	6.51	IC50	312	nM	CHEMBL_ACT_19197975
DHODH	6.5	IC50	320	nM	CHEMBL_ACT_19258670
DHODH	6.45	IC50	356	nM	CHEMBL_ACT_16597667
DHFR	6.41	IC50	388	nM	CHEMBL_ACT_18027785
DHODH	6.41	IC50	388	nM	CHEMBL_ACT_18337161
DHODH	6.39	IC50	407.8	nM	CHEMBL_ACT_24820946
DHODH	6.39	IC50	407.8	nM	CHEMBL_ACT_25582348
DHODH	6.38	IC50	420	nM	CHEMBL_ACT_1602498
DHODH	6.36	IC50	440	nM	CHEMBL_ACT_14734111

Target pathways

Aggregated over 1 target gene(s): DHODH.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Pyrimidine biosynthesis	1	DHODH

Dominant GO biological processes

GO term	Targets
‘de novo’ pyrimidine nucleobase biosynthetic process	1
UDP biosynthetic process	1
pyrimidine ribonucleotide biosynthetic process	1
‘de novo’ UMP biosynthetic process	1
pyrimidine nucleotide biosynthetic process	1
UMP biosynthetic process	1

Indications & clinical

Indications

7 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
multiple sclerosis	4	MONDO:0005301	MONDO:0005301
relapsing-remitting multiple sclerosis	4	MONDO:0005314	EFO:0003929
secondary progressive multiple sclerosis	3	MONDO:0000450	EFO:0008522
autoimmune thrombocytopenic purpura	2	MONDO:0008558	EFO:0007160
kidney disorder	1	MONDO:0005240	EFO:0003086
celiac disease	1	MONDO:0005130	EFO:0001060
tropical spastic paraparesis	1	MONDO:0008039	EFO:0007527

Clinical trials

Total trials: 56.

Phase distribution

Phase	Trials
PHASE3	26
PHASE2	11
Not specified	9
PHASE4	5
PHASE1	3
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01895335	PHASE4	COMPLETED	Using Patient Reported Outcomes (PROs) to Evaluate Teriflunomide Treatment in Relapsing Multiple Sclerosis (RMS) Patients
NCT01970410	PHASE4	COMPLETED	MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV
NCT03856619	PHASE4	COMPLETED	To Evaluate the Safety and Efficacy of Teriflunomide in Patients With Relapsing Forms of Multiple Sclerosis
NCT04129736	PHASE4	COMPLETED	Teriflunomide Concentration in Serum and Cerebrospinal Fluid From Patients With Multiple Sclerosis
NCT04410965	PHASE4	COMPLETED	Evaluation of the Relationship Between ABCG2 Mutation and Teriflunomide Exposure and Safety in Chinese RMS Patients Treated With Teriflunomide 14 mg Once Daily for 24 Weeks
NCT04586010	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
NCT04586023	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
NCT05147220	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)
NCT05156281	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)
NCT06141473	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis
NCT06372145	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.
NCT07189325	PHASE3	NOT_YET_RECRUITING	A Prospective Randomized Non-inferiority Trial Comparing Anti-CD20 Maintenance Versus De-Escalation Strategy In Relapsing-Remitting Multiple Sclerosis
NCT00134563	PHASE3	COMPLETED	Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis
NCT00622700	PHASE3	COMPLETED	Phase III Study With Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis
NCT00751881	PHASE3	COMPLETED	An Efficacy Study of Teriflunomide in Participants With Relapsing Multiple Sclerosis
NCT00803049	PHASE3	COMPLETED	Long Term Safety and Efficacy Study of Teriflunomide 7 mg or 14 mg in Patients With Relapsing-Remitting Multiple Sclerosis
NCT00883337	PHASE3	COMPLETED	A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis
NCT01252355	PHASE3	TERMINATED	Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis and Treated With Interferon-beta
NCT01863888	PHASE3	COMPLETED	Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis
NCT02201108	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis
NCT02425644	PHASE3	COMPLETED	Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis
NCT02587195	PHASE3	COMPLETED	A Study to Evaluate the Safety of Long Term Treatment With Teriflunomide 14 mg Once Daily in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis in a Long-term Extension Period
NCT02792218	PHASE3	COMPLETED	Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis
NCT02792231	PHASE3	COMPLETED	Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis.
NCT03277248	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (RMS)
NCT03277261	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (RMS) ( ULTIMATE 1 )
NCT04338022	PHASE3	TERMINATED	Study of Evobrutinib in Participants With RMS (evolutionRMS 1)
NCT04338061	PHASE3	TERMINATED	Study of Evobrutinib in Participants With RMS (evolutionRMS 2)
NCT04410978	PHASE3	COMPLETED	Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)
NCT04410991	PHASE3	COMPLETED	Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 2)
NCT05385744	PHASE3	COMPLETED	An International, Multicenter, Randomized, Double-Blind, Double-Masked Study of the Efficacy and Safety of BCD-132 (JSC BIOCAD, Russia) Using an Active Reference Drug (Teriflunomide) for the Treatment of Patients With Multiple Sclerosis
NCT04799288	PHASE1/PHASE2	RECRUITING	Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
NCT07065968	PHASE2	RECRUITING	The Efficacy and Safety of Combined Teriflunomide and High-dose Dexamethasone in Newly Diagnosed Primary Immune Thrombocytopenia (TEMPO-2)
NCT00228163	PHASE2	COMPLETED	Long Term Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
NCT00475865	PHASE2	COMPLETED	Phase II Study of Teriflunomide as Adjunctive Therapy to Glatiramer Acetate in Subjects With Multiple Sclerosis
NCT00489489	PHASE2	COMPLETED	Phase II Study of Teriflunomide as Adjunctive Therapy to Interferon-beta in Subjects With Multiple Sclerosis
NCT00811395	PHASE2	COMPLETED	Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis
NCT01403376	PHASE2	COMPLETED	Study to Investigate the Immune Response to Influenza Vaccine in Patients With Multiple Sclerosis on Teriflunomide
NCT01487096	PHASE2	COMPLETED	Safety and Efficacy of Teriflunomide (HMR1726) in Multiple Sclerosis With Relapses
NCT04056897	PHASE2	COMPLETED	Comparative Study of the Efficacy and Safety of BCD-132 With Teriflunomide and Placebo in Multiple Sclerosis

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

10 molecules share ≥1 primary target. Top 10 by shared-target count:

Molecule	Source	Status	Shared targets
ATOVAQUONE	ChEMBL	Phase 4 (approved)	DHODH
LEFLUNOMIDE	ChEMBL	Phase 4 (approved)	DHODH
VIDOFLUDIMUS	ChEMBL	Phase 3	DHODH
ASLAN-003	ChEMBL	Phase 2	DHODH
BREQUINAR	ChEMBL	Phase 2	DHODH
CLONIXIN	ChEMBL	Phase 2	DHODH
FLUNIXIN	ChEMBL	Phase 2	DHODH
NIFLUMIC ACID	ChEMBL	Phase 2	DHODH
OXYCINCHOPHEN	ChEMBL	Phase 2	DHODH
PIPERINE	ChEMBL	Phase 2	DHODH