Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohns disease and lupus. Specifically it is used following kidney, heart, and liver transplantation. It can be given by mouth or by injection into a vein. It comes as mycophenolate sodium and mycophenolate mofetil.Common side effects include nausea, infections, and diarrhea. Other serious side effects include an increased risk of cancer, progressive multifocal leukoencephalopathy, anemia, and gastrointestinal bleeding. Use during pregnancy may harm the baby. It works by blocking inosine monophosphate dehydrogenase (IMPDH), which is needed by lymphocytes to make guanosine.Mycophenolic acid was initially discovered by Italian Bartolomeo Gosio in 1893. It was rediscovered in 1945 and 1968. It was approved for medical use in the United States in 1995 following the discovery of its immunosuppressive properties in the 1990s. It is available as a generic medication. In 2017, it was the 254th most commonly prescribed medication in the United States, with more than one million prescriptions. Medical uses
Organ transplant
Mycophenolate is used for the prevention of organ transplant rejection. Mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and kidney transplantation rejection in children over 2 years; whereas mycophenolate sodium is indicated for the prevention of kidney transplant rejection in adults. Mycophenolate sodium has also been used for the prevention of rejection in liver, heart, or lung transplants in children older than two years.
In contrast, many other cell types use both pathways, and some cells, such as terminally differentiated neurons, depend completely on purine nucleotide salvage. Thus, use of mycophenolic acid leads to a relatively selective inhibition of DNA replication in T cells and B cells. Pharmacology
Mycophenolate can be derived from the fungi Penicillium stoloniferum, P. brevicompactum and P. echinulatum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It reversibly inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes. Other cells recover purines via a separate salvage pathway and are thus able to escape the effect.Mycophenolate is potent and can, in many contexts, be used in place of the older anti-proliferative azathioprine. It is usually used as part of a three-compound regimen of immunosuppressants, also including a calcineurin inhibitor (ciclosporin or tacrolimus) and a glucocorticoid (e.g. dexamethasone or prednisone). Chemistry
Mycophenolate mofetil is the morpholino‌ ethyl ester of mycophenolic acid; the ester masks the carboxyl group. Mycophenolate mofetil is reported to have a pKa values of 5.6 for the morpholino moiety and 8.5 for the phenolic group. History
Mycophenolic acid was discovered by Italian medical scientist Bartolomeo Gosio. Gosio collected a fungus from spoiled corn and named it Penicillium glaucum. (The species is now called P. brevicompactum.) In 1893 he found that the fungus had antibacterial activity.