Various immunosuppressive, antineoplastic, and antibiotic drugs function by interfering with nucleotide synthesis:
- Pyrimidine synthesis:
- Leflunomide: inhibits dihydroorotate dehydrogenase
- Methotrexate (MTX), trimethoprim (TMP), and pyrimethamine: inhibit dihydrofolate reductase (↓deoxythymidine monophosphate [dTMP]) in humans, bacteria, and protozoa, respectively
- 5-fluorouracil (5-FU) and its prodrug capecitabine: form 5-F-dUMP, which inhibits thymidylate synthase (↓ dTMP)
- Purine synthesis:
- 6-mercaptopurine (6-MP) and its prodrug azathioprine: inhibit de novo purine synthesis
- Mycophenolate and ribavirin: inhibit inosine monophosphate dehydrogenase
- Purine and pyrimidine synthesis:
- Hydroxyurea: inhibits ribonucleotide reductase