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Chemical Compound Review

Leflunomid     5-methyl-N-[4- (trifluoromethyl)phenyl]- 1,2...

Synonyms: lefunamide, Arava, Leflunomida, Repso, SULOL, ...
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Disease relevance of leflunomide


High impact information on leflunomide


Chemical compound and disease context of leflunomide


Biological context of leflunomide


Anatomical context of leflunomide

  • These findings were supported by the results in which leflunomide administration decreased the number of T lymphocytes infiltrating the liver as well as inhibiting their production of TNF-alpha [2].
  • Treatment with leflunomide markedly reduced serum transaminase activities and the numbers of dead liver cells [2].
  • The mechanism of protection by leflunomide was not through inhibition of cytochrome P450 (CYP)-catalyzed APAP bioactivation or an apparent suppression of the innate immune system [3].
  • Hence, after 4 wk of LF, the rats developed partial B cell tolerance, as they were unable to produce T-independent (CsA-resistant) XAbs [19].
  • Moreover, splenocytes taken from rats that rejected Xgs despite a treatment with LF + ASGM-1 provoked an acceleration of Xg rejection when transferred to newly transplanted LF + ASGM-1-treated nude rats, and finally, the latter accelerating effect disappeared when macrophages were first depleted from the adoptively transferred splenocytes [20].

Associations of leflunomide with other chemical compounds


Gene context of leflunomide


Analytical, diagnostic and therapeutic context of leflunomide


  1. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Smolen, J.S., Kalden, J.R., Scott, D.L., Rozman, B., Kvien, T.K., Larsen, A., Loew-Friedrich, I., Oed, C., Rosenburg, R. Lancet (1999) [Pubmed]
  2. Leflunomide protects from T-cell-mediated liver injury in mice through inhibition of nuclear factor kappaB. Imose, M., Nagaki, M., Kimura, K., Takai, S., Imao, M., Naiki, T., Osawa, Y., Asano, T., Hayashi, H., Moriwaki, H. Hepatology (2004) [Pubmed]
  3. Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury. Latchoumycandane, C., Goh, C.W., Ong, M.M., Boelsterli, U.A. Hepatology (2007) [Pubmed]
  4. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial. Kaltwasser, J.P., Nash, P., Gladman, D., Rosen, C.F., Behrens, F., Jones, P., Wollenhaupt, J., Falk, F.G., Mease, P. Arthritis Rheum. (2004) [Pubmed]
  5. Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. Suissa, S., Hudson, M., Ernst, P. Arthritis Rheum. (2006) [Pubmed]
  6. Induction of specific transplantation tolerance across xenogeneic barriers in the T-independent immune compartment. Lin, Y., Goebels, J., Xia, G., Ji, P., Vandeputte, M., Waer, M. Nat. Med. (1998) [Pubmed]
  7. Leflunomide in treatment of rheumatoid arthritis. McCarey, D.W., Capell, H.A., Madhok, R. Lancet (2002) [Pubmed]
  8. Rational use of new and existing disease-modifying agents in rheumatoid arthritis. Kremer, J.M. Ann. Intern. Med. (2001) [Pubmed]
  9. Leflunomide and peripheral neuropathy: a potential interaction between uracil/tegafur and leflunomide. Kopp, H.G., Moerike, K., Kanz, L., Hartmann, J.T. Clin. Pharmacol. Ther. (2005) [Pubmed]
  10. Leflunomide-mediated suppression of antiviral antibody and Tcell responses: differential restoration by uridine. Pinschewer, D.D., Ochsenbein, A.F., Fehr, T., Zinkernagel, R.M. Transplantation (2001) [Pubmed]
  11. BK virus nephritis after renal transplantation. Hariharan, S. Kidney Int. (2006) [Pubmed]
  12. Inhibition of HIV replication by A77 1726, the active metabolite of leflunomide, in combination with pyrimidine nucleoside reverse transcriptase inhibitors. Hossain, M.M., Margolis, D.M. J. Acquir. Immune Defic. Syndr. (2001) [Pubmed]
  13. Therapeutic options for resistant lupus nephritis. Mok, C.C. Semin. Arthritis Rheum. (2006) [Pubmed]
  14. Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgG1 production. Siemasko, K., Chong, A.S., Jäck, H.M., Gong, H., Williams, J.W., Finnegan, A. J. Immunol. (1998) [Pubmed]
  15. Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Weinblatt, M.E., Kremer, J.M., Coblyn, J.S., Maier, A.L., Helfgott, S.M., Morrell, M., Byrne, V.M., Kaymakcian, M.V., Strand, V. Arthritis Rheum. (1999) [Pubmed]
  16. Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. Xu, X., Williams, J.W., Bremer, E.G., Finnegan, A., Chong, A.S. J. Biol. Chem. (1995) [Pubmed]
  17. Bruton's tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex. Vassilev, A., Ozer, Z., Navara, C., Mahajan, S., Uckun, F.M. J. Biol. Chem. (1999) [Pubmed]
  18. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. Manna, S.K., Aggarwal, B.B. J. Immunol. (1999) [Pubmed]
  19. Accommodation and T-independent B cell tolerance in rats with long term surviving hamster heart xenografts. Lin, Y., Vandeputte, M., Waer, M. J. Immunol. (1998) [Pubmed]
  20. Natural killer cell- and macrophage-mediated rejection of concordant xenografts in the absence of T and B cell responses. Lin, Y., Vandeputte, M., Waer, M. J. Immunol. (1997) [Pubmed]
  21. Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis. Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers. Kraan, M.C., Reece, R.J., Barg, E.C., Smeets, T.J., Farnell, J., Rosenburg, R., Veale, D.J., Breedveld, F.C., Emery, P., Tak, P.P. Arthritis Rheum. (2000) [Pubmed]
  22. The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms. Elder, R.T., Xu, X., Williams, J.W., Gong, H., Finnegan, A., Chong, A.S. J. Immunol. (1997) [Pubmed]
  23. The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells c1. Urushibara, M., Takayanagi, H., Koga, T., Kim, S., Isobe, M., Morishita, Y., Nakagawa, T., Löeffler, M., Kodama, T., Kurosawa, H., Taniguchi, T. Arthritis Rheum. (2004) [Pubmed]
  24. Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal protein kinase, and apoptosis. Manna, S.K., Mukhopadhyay, A., Aggarwal, B.B. J. Immunol. (2000) [Pubmed]
  25. Effects of leflunomide on hyaluronan synthases (HAS): NF-kappa B-independent suppression of IL-1-induced HAS1 transcription by leflunomide. Stuhlmeier, K.M. J. Immunol. (2005) [Pubmed]
  26. Suppression of experimental autoimmune neuritis by leflunomide. Korn, T., Toyka, K., Hartung, H.P., Jung, S. Brain (2001) [Pubmed]
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