What is the MOA of MMF?
MMF is an inactive prodrug that is hydrolyzed to active MPA. MPA is a reversible inhibitor of inosine-5’-monophosphate dehydrogenase (IMPDH), which is an enzyme necessary for the de novo synthesis of the purine, guanosine. Lymphocytes (T and B cells) depend on IMPDH to generate sufficient guanosine levels to initiate a proliferative response to antigen. Cytokine production is not affected. MPA also inhibits carbohydrate (fucose, mannose) transfer to glycoproteins, resulting in less production of adhesion molecules (VLA-4, ICAM-1). In summary, MPA inhibits lymphocyte proliferation and migration. It also has antifibrotic activity. Notably, neutrophils are less affected by MPA than lymphocytes. The enterohepatic recycling of glucuronide-conjugated MPA contributes to GI toxicity since GI mucosal cells are 50% dependent upon de novo synthesis pathway of purines, which is inhibited by MPA.
