Compound Detail

CHEMBL960

LEFLUNOMIDE

💊 Approved Drug

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💊 Approved Drug

Cc1oncc1C(=O)Nc1ccc(C(F)(F)F)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL960
Name	LEFLUNOMIDE
Phase	Approved
Structure Type	MOL
InChI Key	VHOGYURTWQBHIL-UHFFFAOYSA-N
Therapeutic	✓ Yes
Active Moiety	CHEMBL973

Known Names

Arava HWA-486 L04AA13 Leflunomida Leflunomide Leflunomide medac Leflunomide ratiopharm Leflunomide teva Leflunomide winthrop Leflunomide zentiva (previously leflunomide winthrop) NSC-677411 NSC-759864 +4 more

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

270.2

MW (Da)

3.25

ALogP

HBA

HBD

55.1

PSA (Å²)

0.91

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1998
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Black Box Warning Prodrug

USAN Year

1998

Extended Properties

Molecular Formula	C12H9F3N2O2
MW	270.21
Aromatic Rings	2
Heavy Atoms	19
NP-Likeness	-2.04

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Dihydroorotate dehydrogenase inhibitor	INHIBITOR	Dihydroorotate dehydrogenase (quinone), mitochondrial	✓	✓

Indications

Arthritis, Psoriatic Arthritis, Rheumatoid Central Nervous System Neoplasms Lupus Nephritis Myasthenia Gravis Polymyalgia Rheumatica Severe Acute Respiratory Syndrome IgA Vasculitis Lupus Erythematosus, Systemic Lymphoproliferative Disorders Multiple Myeloma Pemphigoid, Bullous Prostatic Neoplasms, Castration-Resistant Sjogren's Syndrome Smoldering Multiple Myeloma Uveitis Breast Diseases Breast Neoplasms Breast Neoplasms Bronchiolitis Obliterans Syndrome

ATC Classification

L04AK01

leflunomide

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: IMMUNOSUPPRESSANTS

Drug Warnings

Black Box Warning

teratogenicity

Country: United States

Black Box Warning

hepatotoxicity

Country: United States

Activity Summary

IC50 49 meas. best 8.05

EC50 3 meas. best 5.25

Ki 3 meas. best 5.64

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Dihydroorotate dehydrogenase (quinone), mitochondrial CHEMBL2383	IC50	8.05	6.925	9.0	2
Dihydroorotate dehydrogenase (quinone), mitochondrial CHEMBL2991	IC50	7.52	7.52	30.0	1
Cytochrome P450 1A2 CHEMBL3356	IC50	6.3	6.3	500.0	1
Dihydroorotate dehydrogenase (quinone), mitochondrial CHEMBL1966	IC50	6.1	5.33	800.0	3
Rattus norvegicus CHEMBL376	IC50	6.0	6.0	1000.0	1
Sodium-dependent dopamine transporter CHEMBL238	Ki	5.64	5.64	2291.0	1
Sodium-dependent dopamine transporter CHEMBL238	IC50	5.54	5.54	2884.0	1
Sodium-dependent noradrenaline transporter CHEMBL222	Ki	5.34	5.34	4591.0	1
Sodium-dependent noradrenaline transporter CHEMBL222	IC50	5.33	5.33	4630.0	1
Mus musculus CHEMBL375	IC50	5.29	5.076	5100.0	5
Unchecked CHEMBL612545	IC50	5.29	4.7125	5100.0	4
Unchecked CHEMBL612545	Ki	5.29	5.29	5159.0	1
Homo sapiens CHEMBL372	IC50	5.27	5.27	5400.0	1
Nucleic Acid CHEMBL345	EC50	5.25	5.25	5650.0	1
Serine/threonine-protein kinase pim-3 CHEMBL5407	IC50	4.69	4.69	20600.0	1
Amine oxidase [flavin-containing] A CHEMBL1951	IC50	4.68	4.68	20696.0	1
Leishmania donovani CHEMBL367	IC50	4.66	4.66	21760.0	1
Serine/threonine-protein kinase pim-1 CHEMBL2147	IC50	4.54	4.54	28700.0	1
HT-1080 CHEMBL614580	IC50	4.52	4.47	30000.0	2
MIA PaCa-2 CHEMBL614725	IC50	4.5	4.5	32000.0	1
BXPC-3 CHEMBL614530	IC50	4.5	4.5	32000.0	1
West Nile virus CHEMBL613730	EC50	4.46	4.46	35020.0	1
Jurkat CHEMBL397	IC50	4.46	4.42	34600.0	2
Cytomegalovirus CHEMBL613134	EC50	4.4	4.4	40000.0	1
PANC-1 CHEMBL614139	IC50	4.33	4.33	47000.0	1
MCF7 CHEMBL387	IC50	4.26	4.25	55000.0	2
HT-29 CHEMBL384	IC50	4.12	4.12	75000.0	2
M21 CHEMBL614117	IC50	4.08	4.08	83000.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	23.99	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	3.0	uL.min-1.(10^6cells)-1	Homo sapiens
T1/2	0.4	hr	-
T1/2	1.167	hr	-

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Dihydroorotate dehydrogenase (quinone), mitochondrial	IC50	=	9.0	nM	8.05	Inhibitory concentration tested against enzyme dihydroorotate dehydrogenase in r...	8917650
Dihydroorotate dehydrogenase (quinone), mitochondrial	IC50	=	30.0	nM	7.52	Inhibitory concentration tested on enzyme dihydroorotate dehydrogenase in mouse	8917650
Cytochrome P450 1A2	IC50	=	500.0	nM	6.3	DRUGMATRIX: CYP450, 1A2 enzyme inhibition (substrate: 3-Cyano-7-ethoxycoumarin)	-
Dihydroorotate dehydrogenase (quinone), mitochondrial	IC50	=	800.0	nM	6.1	Inhibition of human DHODH	34116160
Rattus norvegicus	IC50	=	1000.0	nM	6.0	Immunosuppressant activity in rat using mixed leukocyte response (MLR).	9873623
Dihydroorotate dehydrogenase (quinone), mitochondrial	IC50	=	1600.0	nM	5.8	Inhibition of DHODH in Wistar rat liver homogenates by DCIP reduction assay	21109332
Sodium-dependent dopamine transporter	Ki	=	2291.0	nM	5.64	DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)	-
Sodium-dependent dopamine transporter	IC50	=	2884.0	nM	5.54	DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)	-
Sodium-dependent noradrenaline transporter	Ki	=	4591.0	nM	5.34	DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-5...	-
Sodium-dependent noradrenaline transporter	IC50	=	4630.0	nM	5.33	DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-5...	-
Mus musculus	IC50	=	5100.0	nM	5.29	In vitro inhibitory activity against murine antibody response to T-cell independ...	9719606
Unchecked	IC50	=	5100.0	nM	5.29	In vitro inhibition of Ab formation from trinitrophenyl-lipopolysaccharide (TNP-...	11384243
Unchecked	Ki	=	5159.0	nM	5.29	DRUGMATRIX: Sodium/nucleoside co-transporter radioligand binding (ligand: nitrob...	-
Homo sapiens	IC50	=	5400.0	nM	5.27	Immunosuppressant activity using human mixed leukocyte response (HMLR).	9873623
Nucleic Acid	EC50	=	5650.0	nM	5.25	PUBCHEM_BIOASSAY: Luminescent HTS for small molecule inhibitors of MT1-MMP trans...	-
Mus musculus	IC50	=	7400.0	nM	5.13	In vitro inhibitory activity against mouse mixed lymphocyte reaction (MLR)	9719606
Mus musculus	IC50	=	9600.0	nM	5.02	The compound was tested for in vitro mixed lymphocyte reaction.	9207942
Mus musculus	IC50	=	10000.0	nM	5.0	Compound was tested in vitro for immunosuppressive activity which was measured i...	9873513
Dihydroorotate dehydrogenase (quinone), mitochondrial	IC50	=	10000.0	nM	5.0	Immunosuppressive activity expressed as ability to inhibit human recombinant dih...	9873513
Mus musculus	IC50	=	11400.0	nM	4.94	In vitro T-cell immunosuppressive activity in the mouse mixed lymphocyte reactio...	11384243

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL3885881	Rattus norvegicus	581
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
11384243	10.1021/jm010822m	Mus musculus	12
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
-	10.6019/CHEMBL4689842	HEK-293T	10
-	10.6019/CHEMBL4689842	Fibroblast	9
-	10.6019/CHEMBL4689842	U2OS	8
15646539	10.1016/s0399-8320(04)95062-2	NON-PROTEIN TARGET	8
-	10.6019/CHEMBL5209801	Alpha-2A adrenergic receptor	5
-	10.6019/CHEMBL5209801	CX3C chemokine receptor 1	5
-	10.6019/CHEMBL5209801	Beta-2 adrenergic receptor	5
-	10.6019/CHEMBL5209801	Adhesion G-protein coupled receptor F1	5
-	10.6019/CHEMBL5209801	Glucose-dependent insulinotropic receptor	5
-	10.6019/CHEMBL5209801	Type-1 angiotensin II receptor	5
-	10.6019/CHEMBL5209801	Apelin receptor	5
-	10.6019/CHEMBL5209801	Glucagon-like peptide 1 receptor	5
-	10.6019/CHEMBL5209801	Sphingosine 1-phosphate receptor 1	5
-	10.6019/CHEMBL5209801	Free fatty acid receptor 4	5
-	10.6019/CHEMBL5209801	C5a anaphylatoxin chemotactic receptor 1	5
-	10.6019/CHEMBL5209801	N-formyl peptide receptor 2	5

Data from ChEMBL 36 via Core Engine