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Inosine monophosphate dehydrogenase inhibitors

Mycophenolic acid obtained from Penicillium culture is an inhibitor of inosine monophosphate dehydrogenase, enzyme responsible of the conversion of inosine monophosphate, IMP, into xanthosine monophosphate, XMP, precursor of guanosine derivatives.

Role of the inosine monophosphate dehydrogenase

This inhibition induces a decrease of the synthesis of guanosine monophosphate, GMP, whose intracellular concentration falls as well as that of its metabolites guanosine triphosphate, GTP, and deoxyguanosine triphosphate, dGTP, necessary to the synthesis of RNA and DNA. The fall of GTP which it elicits disturbs moreover the transfer of fucose and mannose on glycoproteins involved in cellular adhesion.

Mycophenolic acid is particularly active on B and T- cells and inhibits their proliferation. It inhibits the production of antibodies

Mycophenolic acid esterified to increase its bioavailability is named mycophenolate mofetil (Cellcept*) used as immunosuppressant for preventing acute rejections of organ transplants. It has other clinical uses in the treatment of immunologic diseases.

Its main adverse effects are hematological (neutropenia) and infections because of immunosuppression. Its prolonged use would increase the risk of lymphoma and other malignant tumors. It is teratogenic in animals.

Mycophenolic acid
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