DHODH inhibitor
Dihydroorotate dehydrogenase inhibitor
- ↓ de novo pyrimidine synthesis
- Rapidly dividing lymphocytes cannot rely on salvage alone → immunomodulation
- Teratogenic
- Hepatotoxicity; 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.
Self-check
- Which nucleotide synthesis pathway does DHODH inhibition reduce?
De novo pyrimidine synthesis. - Why are rapidly dividing lymphocytes affected by DHODH inhibition?
They cannot rely on salvage alone.
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