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