II. Indications

  1. See Antimetabolite Chemotherapy for Purine Analog related indications in cancer
  2. Solid Organ Transplant Immunosuppression (maintenance prevention of rejection)
  3. Autoimmune Conditions (e.g. IgA nephropathy, lupus erythematosus, Nephrotic Syndrome, Crohns Disease)

III. Medications: Inosine monophosphate dehydrogenase (IMPDH) Inhibitors

  1. Mechanism
    1. Inosine monophosphate dehydrogenase (IMPDH)
      1. IMPDH is key to conversion of inosine monophosphate (IMP) to guanosine monophosphate (GMP)
      2. Guanosine monophosphate (GMP) is in turn converted to the guanine purine Nucleotides (GDP, GTP, and dGTP)
      3. Guanine purine Nucleotide is key to DNA and RNA synthesis, as well as Energy Metabolism (GTP)
    2. IMPDH Inhibitors decrease DNA and RNA synthesis
      1. IMPDH effects de novo Purine synthesis but not the salvage pathway Purine synthesis
      2. Lymphocytes are selectively affected, as they rely on de novo Purine synthesis of guanine
  2. Inosine monophosphate dehydrogenase (IMPDH) Inhibitors
    1. Mycophenolate (Cellcept)
    2. Mizoribine (MZ)

IV. Medications: Analog Purine Synthesis Inhibitors

  1. See Antimetabolite Chemotherapy
  2. Mechanism
    1. Purine Analogs, resembling adenine or guanine, and incorporate into DNA
    2. Result in DNA cross-linking and inhibition of synthesis and repair of DNA
  3. Purine Analogs
    1. Azathioprine (Imuran)
    2. Cladribine (Leustatin)
    3. Clofarabine
    4. Fludarabine (Fludara)
    5. Mercaptopurine (6-MP, Purinethol)
    6. Nelarabine
    7. Pentostatin (Nipent)
    8. Thioguanine (6-TG)

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