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| http://linked.open...gbank/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. (en)
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| http://linked.open...y/drugbank/dosage
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| http://linked.open...generalReferences
| - # Goldenberg MM: Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther. 1999 Nov;21(11):1837-52; discussion 1821. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/10890256 # Li EK, Tam LS, Tomlinson B: Leflunomide in the treatment of rheumatoid arthritis. Clin Ther. 2004 Apr;26(4):447-59. "Pubmed":http://www.ncbi.nlm.nih.gov/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":http://www.ncbi.nlm.nih.gov/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":http://www.ncbi.nlm.nih.gov/pubmed/11053058\# Reitzik M, Lownie JF: Familial polyostotic fibrous dysplasia. Oral Surg Oral Med Oral Pathol. 1975 Dec;40(6):769-74. "Pubmed":http://www.ncbi.nlm.nih.gov/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":http://www.ncbi.nlm.nih.gov/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":http://www.ncbi.nlm.nih.gov/pubmed/10878295 # Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9666414 (en)
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| http://linked.open...gy/drugbank/group
| - approved (en)
- investigational (en)
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| http://linked.open...drugbank/halfLife
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| http://linked.open...ugbank/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. (en)
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| http://linked.open...mechanismOfAction
| - 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. (en)
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| http://linked.open...drugbank/packager
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| http://linked.open...outeOfElimination
| - 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. (en)
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| http://linked.open.../drugbank/synonym
| - Leflunomide (en)
- Arava (en)
- Leflunomida (en)
- Leflunomidum (en)
- Lefunomide (en)
- alpha,alpha,alpha-Trifluoro-5-methyl-4-isoxazolecarboxy-P-toluidide (en)
- 5-Methyl-N-(4-(trifluoromethyl)phenyl)-4-isoxazolecarboxamide (en)
- 5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide (en)
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| http://linked.open...drugbank/toxicity
| - LD<sub>50</sub>=100-250 mg/kg (acute oral toxicity) (en)
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| http://linked.open...umeOfDistribution
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| http://linked.open.../drug/hasAHFSCode
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| http://linked.open...k/foodInteraction
| - Take without regard to meals. (en)
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| http://linked.open...nk/proteinBinding
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| http://linked.open...ynthesisReference
| - Ilya Avrutov, "Novel processes for making- and a new crystalline form of- leflunomide." U.S. Patent US20010031878, issued October 18, 2001. (en)
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| http://linked.open...y/mesh/hasConcept
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| http://linked.open...ugbank/IUPAC-Name
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| http://linked.open...gy/drugbank/InChI
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| http://linked.open...Molecular-Formula
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| http://linked.open.../Molecular-Weight
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| http://linked.open...noisotopic-Weight
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| http://linked.open...y/drugbank/SMILES
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| http://linked.open.../Water-Solubility
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| http://linked.open...ogy/drugbank/logP
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| http://linked.open...ogy/drugbank/logS
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| http://linked.open...l/drug/hasATCCode
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| http://linked.open...nd-Acceptor-Count
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| http://linked.open...-Bond-Donor-Count
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| http://linked.open...drugbank/InChIKey
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| http://linked.open...urface-Area--PSA-
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| http://linked.open...nk/Polarizability
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| http://linked.open...bank/Refractivity
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| http://linked.open...atable-Bond-Count
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| http://linked.open...ugbank/absorption
| - Well absorbed, peak plasma concentrations appear 6-12 hours after dosing (en)
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| http://linked.open.../affectedOrganism
| - Humans and other mammals (en)
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| http://linked.open...casRegistryNumber
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| http://linked.open...drugbank/category
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| http://linked.open...gbank/containedIn
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| http://linked.open...k/Bioavailability
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| http://linked.open...bank/Ghose-Filter
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| http://linked.open...nk/MDDR-Like-Rule
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| http://linked.open...ank/Melting-Point
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| http://linked.open...k/Number-of-Rings
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| http://linked.open...siological-Charge
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| http://linked.open...bank/Rule-of-Five
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| http://linked.open...tional-IUPAC-Name
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| http://linked.open...strongest-acidic-
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| http://linked.open...-strongest-basic-
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