De Novo Purine and Pyrimidine Synthesis

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

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