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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.
Drug Type: Small Molecule; Approved; Investigational
Pharmacology: 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 an isoxazole immunomodulatory agent which inhibits dihydroorotate dehydrogenase (an enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity. Specifically Leflunomide blocks the de novo synthesis of pyrimidines, thus preventing the proliferation of activated T cells. Several in vivo and in vitro experimental models have demonstrated an anti-inflammatory effect. Following oral administration, leflunomide is metabolized to an active metabolite A77 1726 which is responsible for essentially all of its activity in vivo.
Indication: For the treatment of active rheumatoid arthritis (RA).
Half Life: 2 weeks
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Data Correlations | 3 studies

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Genes category icon Genes
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DHODH 100 100
CYP1A1 100 100
Mbl1 94 94
PDIA3 92 92
PON1 92 92
HRK 90 90
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Biogroups category icon Biogroups
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Rhodopsin Like 100 100
GPCR, family 2, secretin-like 99 99
Pyrimidine Metabolism 98 98
Gamma Hexachlorocyclohexane Degrada… 98 98
RmlC-like jelly roll fold 97 97
G-Protein Signaling Pathway 97 97
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  • Walter H Hörl
  • Jun Li
  • B Rozman
  • Gerhard J Zlabinger
  • Vibeke Strand
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