DHODH inhibitor
Dihydroorotate dehydrogenase inhibitor
- ↓ de novo pyrimidine synthesis
- Rapidly dividing lymphocytes cannot rely on salvage alone → immunomodulation
- Teratogenic
- Blocks pyrimidine synthesis in proliferating lymphocytes
- Hepatotoxicity; teratogenic with a very long half-life
Drugs with this mechanism (2)
- Leflunomide — DMARD inhibiting pyrimidine synthesis for rheumatoid arthritis; long half-life.
- Teriflunomide — Active metabolite of leflunomide, marketed for MS; long washout needs cholestyramine.
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