The Sound of Evolution
Leflunomide
Mechanism of action:
Leflunomide itself is a prodrug that is rapidly converted in the body into its major active metabolite, teriflunomide (A77 1726). Teriflunomide selectively inhibits dihydroorotate dehydrogenase, an enzyme located in the mitochondrion and involved in the de novo synthesis pathway of pyrimidine nucleotides. When dihydroorotate dehydrogenase is inhibited by teriflunomide, de novo pyrimidine nucleotide synthesis decreases, leading to restricted DNA and RNA synthesis.
Reference(s):
1. Goldenberg MM et al. (1999). Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Clin Ther.
2. Li EK et al. (2004). Leflunomide in the treatment of rheumatoid arthritis. Clin Ther.
3. Sanders S et al. (2002). Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am J Med Sci.