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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Leflunomide
- Accession Number
- DB01097 (APRD00205)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Leflunomide is a pyrimidine synthesis inhibitor belonging to the DMARD (disease-modifying antirheumatic drug) class of drugs, which are chemically and pharmacologically very heterogeneous. Leflunomide was approved by FDA and in many other countries (e.g., Canada, Europe) in 1999.
- Structure
Structure for Leflunomide (DB01097)
- Synonyms
- 5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide
- 5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide
- alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-P-toluidide
- Leflunomida
- Leflunomide
- Leflunomidum
- Lefunomide
- External IDs
- L04AA13 / SU-101 / SU101
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Arava Tablet, film coated 20 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU 
Arava Tablet, film coated 10 mg/1 Oral Physicians Total Care, Inc. 2003-08-25 2011-06-30 US 
Arava Tablet, film coated 20 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU Arava Tablet, film coated 10 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU Arava Tablet, film coated 10 mg/1 Oral sanofi-aventis U.S. LLC 1998-09-10 Not applicable US Arava Tablet, film coated 20 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU Arava Tablet, film coated 20 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU Arava Tablet, film coated 10 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU Arava Tablet, film coated 100 mg/1 Oral sanofi-aventis U.S. LLC 1998-09-19 Not applicable US Arava Tablet, film coated 100 mg Oral Sanofi Aventis Deutschland Gmb H 1999-09-02 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Apo-leflunomide Tablet 10 mg Oral Apotex Corporation 2004-09-14 Not applicable Canada 
Apo-leflunomide Tablet 20 mg Oral Apotex Corporation 2004-09-14 Not applicable Canada Dom-leflunomide Tablet 20 mg Oral Dominion Pharmacal Not applicable Not applicable Canada Dom-leflunomide Tablet 10 mg Oral Dominion Pharmacal Not applicable Not applicable Canada Leflunomide Tablet 20 mg/1 Oral Par Pharmaceutical 2007-09-24 2009-09-22 US Leflunomide Tablet 10 mg/1 Oral Alembic Pharmaceuticals Limited 2016-12-01 Not applicable US Leflunomide Tablet 20 mg/1 Oral North Star Rx Llc 2011-05-06 2018-10-19 US 
Leflunomide Tablet 10 mg/1 Oral Golden State Medical Supply 2005-09-13 2018-10-11 US Leflunomide Tablet, film coated 10 mg/1 Oral Barr Laboratories 2005-09-14 2011-09-30 US Leflunomide Tablet 20 mg/1 Oral Trigen Laboratories, Inc. 2011-05-06 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (10 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU Leflunomide Teva Leflunomide (20 mg) Tablet, film coated Oral Teva Pharma B.V. 2011-03-10 2014-03-18 EU - International/Other Brands
- Arava
- Categories
- Adjuvants
- Adjuvants, Immunologic
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Disease-modifying Antirheumatic Agents
- Enzyme Inhibitors
- Immunologic Factors
- Immunosuppressive Agents
- Selective Immunosuppressants
- UNII
- G162GK9U4W
- CAS number
- 75706-12-6
- Weight
- Average: 270.2073
Monoisotopic: 270.061612157 - Chemical Formula
- C12H9F3N2O2
- InChI Key
- VHOGYURTWQBHIL-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)
- IUPAC Name
- 5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide
- SMILES
- CC1=C(C=NO1)C(=O)NC1=CC=C(C=C1)C(F)(F)F
Pharmacology
- Indication
For the management of the signs and symptoms of active rheumatoid arthritis (RA) to improve physical function and to slow the progression of structural damage associated with the disease. Has also been used for the prevention of acute and chronic rejection in recipients of solid organ trasnplants and is designated by the FDA as an orphan drug for this use.
- Associated Conditions
- Pharmacodynamics
Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis.
- Mechanism of action
Leflunomide is a prodrug that is rapidly and almost completely metabolized following oral administration to its pharmacologically active metabolite, A77 1726. This metabolite is responsible for essentially all of the drug's activity in-vivo. The mechanism of action of leflunomide has not been fully determined, but appears to primarily involve regulation of autoimmune lymphocytes. It has been suggested that leflunomide exerts its immunomodulating effects by preventing the expansion of activated autoimmune lymphocytes via interferences with cell cycle progression. In-vitro data indicates that leflunomide interferes with cell cycle progression by inhibiting dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine ribonucleotide uridine monophosphate (rUMP)synthesis) and has antiproliferative activity. Human dihydroorotate dehydrogenase consists of 2 domains: an α/β-barrel domain containing the active site and an α-helical domain that forms a tunnel leading to the active site. A77 1726 binds to the hydrophobic tunnel at a site near the flavin mononucleotide. Inhibition of dihydroorotate dehydrogenase by A77 1726 prevents production of rUMP by the de novo pathway; such inhibition leads to decreased rUMP levels, decreased DNA and RNA synthesis, inhibition of cell proliferation, and G1 cell cycle arrest. It is through this action that leflunomide inhibits autoimmune T-cell proliferation and production of autoantibodies by B cells. Since salvage pathways are expected to sustain cells arrested in the G1 phase, the activity of leflunomide is cytostatic rather than cytotoxic. Other effects that result from reduced rUMP levels include interference with adhesion of activated lymphocytes to the synovial vascular endothelial cells, and increased synthesis of immunosuppressive cytokines such as transforming growth factor-β (TGF-β). Leflunomide is also a tyrosine kinase inhibitor. Tyrosine kinases activate signalling pathways leading to DNA repair, apoptosis and cell proliferation. Inhibition of tyrosine kinases can help to treating cancer by preventing repair of tumor cells.
Target Actions Organism ADihydroorotate dehydrogenase (quinone), mitochondrial inhibitorHuman UAryl hydrocarbon receptor agonistHuman UProtein-tyrosine kinase 2-beta antagonistHuman - Absorption
Well absorbed, peak plasma concentrations appear 6-12 hours after dosing
- Volume of distribution
- 0.13 L/kg
- Protein binding
>99.3%
- Metabolism
Primarily hepatic. Leflunomide is converted to its active form following oral intake.
- Route of elimination
The active metabolite is eliminated by further metabolism and subsequent renal excretion as well as by direct biliary excretion. In a 28 day study of drug elimination (n=3) using a single dose of radiolabeled compound, approximately 43% of the total radioactivity was eliminated in the urine and 48% was eliminated in the feces. It is not known whether leflunomide is excreted in human milk. Many drugs are excreted in human milk, and there is a potential for serious adverse reactions in nursing infants from leflunomide.
- Half life
2 weeks
- Clearance
- Not Available
- Toxicity
LD50=100-250 mg/kg (acute oral toxicity)
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 1A2 --- (C;C) C allele ADR Directly Studied The presence of this genotype in CYP1A2 may be associated with an increased risk of drug-related toxicity from leflunomide therapy. Details
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The therapeutic efficacy of (R)-warfarin can be increased when used in combination with Leflunomide. (S)-Warfarin The therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Leflunomide. 2-Methoxyethanol The risk or severity of adverse effects can be increased when Leflunomide is combined with 2-Methoxyethanol. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Leflunomide. 4-hydroxycoumarin The therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Leflunomide. 6-O-benzylguanine The serum concentration of 6-O-benzylguanine can be increased when it is combined with Leflunomide. 7-Deazaguanine The serum concentration of 7-Deazaguanine can be increased when it is combined with Leflunomide. 7,9-Dimethylguanine The serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Leflunomide. 8-azaguanine The serum concentration of 8-azaguanine can be increased when it is combined with Leflunomide. 8-chlorotheophylline The serum concentration of 8-chlorotheophylline can be increased when it is combined with Leflunomide. - Food Interactions
- Take without regard to meals.
References
- Synthesis Reference
Ilya Avrutov, "Novel processes for making- and a new crystalline form of- leflunomide." U.S. Patent US20010031878, issued October 18, 2001.
US20010031878- General References
- Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. [PubMed:10890256]
- Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743]
- Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. [PubMed:12003373]
- Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. [PubMed:11053058]
- Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033]
- Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. [PubMed:10878294]
- Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. [PubMed:10878295]
- Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414]
- External Links
- Human Metabolome Database
- HMDB0015229
- KEGG Drug
- D00749
- KEGG Compound
- C07905
- PubChem Compound
- 3899
- PubChem Substance
- 46506013
- ChemSpider
- 3762
- BindingDB
- 50054601
- ChEBI
- 6402
- ChEMBL
- CHEMBL960
- Therapeutic Targets Database
- DAP000636
- PharmGKB
- PA450192
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Leflunomide
- ATC Codes
- L04AA13 — Leflunomide
- AHFS Codes
- 92:36.00 — Disease-modifying Antirheumatic Agents
- FDA label
- Download (1.23 MB)
- MSDS
- Download (105 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Apotex Inc.
- Barr Pharmaceuticals
- Diversified Healthcare Services Inc.
- Heritage Pharmaceuticals
- Kali Laboratories Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Physicians Total Care Inc.
- Prasco Labs
- Sandoz
- Sanofi-Aventis Inc.
- Teva Pharmaceutical Industries Ltd.
- Dosage forms
Form Route Strength Tablet, film coated Oral 10 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 100 mg Tablet, film coated Oral 20 mg Tablet Oral 100 mg Tablet Oral 10 mg Tablet Oral 20 mg Tablet Oral 10 mg/1 Tablet Oral 20 mg/1 Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 15 mg - Prices
Unit description Cost Unit Arava 10 mg tablet 24.76USD tablet Arava 20 mg tablet 24.76USD tablet Leflunomide 10 mg tablet 16.75USD tablet Leflunomide 20 mg tablet 16.75USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 165-166 °C Not Available water solubility 21 mg/L (poorly soluble) Not Available logP 2.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0844 mg/mL ALOGPS logP 2.52 ALOGPS logP 2.51 ChemAxon logS -3.5 ALOGPS pKa (Strongest Acidic) 10.41 ChemAxon pKa (Strongest Basic) -0.45 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 55.13 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 64.16 m3·mol-1 ChemAxon Polarizability 23.11 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9949 Caco-2 permeable + 0.5069 P-glycoprotein substrate Non-substrate 0.909 P-glycoprotein inhibitor I Non-inhibitor 0.7822 P-glycoprotein inhibitor II Non-inhibitor 0.8889 Renal organic cation transporter Non-inhibitor 0.9154 CYP450 2C9 substrate Non-substrate 0.8548 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5211 CYP450 1A2 substrate Inhibitor 0.9189 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.5117 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5622 Ames test Non AMES toxic 0.5504 Carcinogenicity Non-carcinogens 0.7067 Biodegradation Not ready biodegradable 0.9836 Rat acute toxicity 3.0297 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9879 hERG inhibition (predictor II) Non-inhibitor 0.9068
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-00di-0390000000-1ac4065d1ef245442a16 MS/MS Spectrum - , positive LC-MS/MS splash10-03di-2920000000-819d0674f452a60be1a4
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Anilides
- Direct Parent
- Aromatic anilides
- Alternative Parents
- Trifluoromethylbenzenes / Isoxazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organofluorides show 3 more
- Substituents
- Aromatic anilide / Trifluoromethylbenzene / Azole / Isoxazole / Heteroaromatic compound / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid derivative / Organoheterocyclic compound / Azacycle show 13 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- monocarboxylic acid amide, isoxazoles, (trifluoromethyl)benzenes (CHEBI:6402)
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ubiquinone binding
- Specific Function
- Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
- Gene Name
- DHODH
- Uniprot ID
- Q02127
- Uniprot Name
- Dihydroorotate dehydrogenase (quinone), mitochondrial
- Molecular Weight
- 42866.93 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. [PubMed:10890256]
- Prakash A, Jarvis B: Leflunomide: a review of its use in active rheumatoid arthritis. Drugs. 1999 Dec;58(6):1137-64. [PubMed:10651393]
- Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. [PubMed:15189743]
- Wozel G, Pfeiffer C: [Leflunomide--a new drug for pharmacological immunomodulation]. Hautarzt. 2002 May;53(5):309-15. [PubMed:12063741]
- Sanders S, Harisdangkul V: Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci. 2002 Apr;323(4):190-3. [PubMed:12003373]
- Breedveld FC, Dayer JM: Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2000 Nov;59(11):841-9. [PubMed:11053058]
- Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. [PubMed:1060033]
- Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology. 2000 May;47(2-3):273-89. [PubMed:10878294]
- Schattenkirchner M: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000 May;47(2-3):291-8. [PubMed:10878295]
- Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. [PubMed:9666414]
- Fukushima R, Kanamori S, Hirashiba M, Hishikawa A, Muranaka RI, Kaneto M, Nakamura K, Kato I: Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Reprod Toxicol. 2007 Nov-Dec;24(3-4):310-6. Epub 2007 May 18. [PubMed:17604599]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Transcription regulatory region dna binding
- Specific Function
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes...
- Gene Name
- AHR
- Uniprot ID
- P35869
- Uniprot Name
- Aryl hydrocarbon receptor
- Molecular Weight
- 96146.705 Da
References
- O'Donnell EF, Saili KS, Koch DC, Kopparapu PR, Farrer D, Bisson WH, Mathew LK, Sengupta S, Kerkvliet NI, Tanguay RL, Kolluri SK: The anti-inflammatory drug leflunomide is an agonist of the aryl hydrocarbon receptor. PLoS One. 2010 Oct 1;5(10). pii: e13128. doi: 10.1371/journal.pone.0013128. [PubMed:20957046]
- Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. [PubMed:17327465]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Signal transducer activity
- Specific Function
- Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulat...
- Gene Name
- PTK2B
- Uniprot ID
- Q14289
- Uniprot Name
- Protein-tyrosine kinase 2-beta
- Molecular Weight
- 115873.62 Da
References
- Pytel D, Sliwinski T, Poplawski T, Ferriola D, Majsterek I: Tyrosine kinase blockers: new hope for successful cancer therapy. Anticancer Agents Med Chem. 2009 Jan;9(1):66-76. [PubMed:19149483]
- Fukushima R, Kanamori S, Hirashiba M, Hishikawa A, Muranaka RI, Kaneto M, Nakamura K, Kato I: Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice. Reprod Toxicol. 2007 Nov-Dec;24(3-4):310-6. Epub 2007 May 18. [PubMed:17604599]
- Steeghs N, Nortier JW, Gelderblom H: Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol. 2007 Feb;14(2):942-53. Epub 2006 Nov 14. [PubMed:17103252]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Sevilla-Mantilla C, Ortega L, Agundez JA, Fernandez-Gutierrez B, Ladero JM, Diaz-Rubio M: Leflunomide-induced acute hepatitis. Dig Liver Dis. 2004 Jan;36(1):82-4. [PubMed:14971821]
- Rozman B: Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet. 2002;41(6):421-30. doi: 10.2165/00003088-200241060-00003. [PubMed:12074690]
- Leflunomide FDA label [File]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423]
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Transporters
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Kis E, Nagy T, Jani M, Molnar E, Janossy J, Ujhellyi O, Nemet K, Heredi-Szabo K, Krajcsi P: Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis. 2009 Jul;68(7):1201-7. doi: 10.1136/ard.2007.086264. Epub 2008 Apr 8. [PubMed:18397960]
Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:32