Azathioprine and MMF

Inhibitors of purine and pyrimidine synthesis

This class of drugs is used for chronic immunosuppression. The two major antimetabolites in clinical use are azathioprine and mycophenolate mofetil (MMF).

Azathioprine and mycophenolate mofetil (MMF) prevent lymphocyte proliferation by way of inhibition of purine base

synthesis, thus resulting in decreased production of building blocks for DNA and RNA.

Azathioprine is metabolized to 6-mercapto purine (6-MP), which is further converted to thioinosine monophosphate (TIMP). This molecule inhibits key enzymes in the de novo pathway of purine synthesis: adenosine monophosphate (AMP) and guanosine monophosphate (GMP).

MMF is metabolized to mycophenolic acid, which is a non-competitive inhibitor of the enzyme that converts inosine monophosphate (IMP) to GMP.

Bone marrow suppression and increased risk of malignancy are the major toxicities associated with antimetabolites. Mycophenolate mofetil is associated with more gastrointestinal side effects than azathioprine.

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Cytotoxic agents such as azathioprine are effective immunosuppressants because they