| Candidate ID: | R0239 |
| Source ID: | DB00688 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Mycophenolate mofetil
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| Synonyms: |
2-morpholinoethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate; Mycophenolate mofetil; Mycophenolic acid morpholinoethyl ester
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| Molecular Formula: |
C23H31NO7
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| SMILES: |
COC1=C(C\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C
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| Structure: |
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| DrugBank Description: |
Mycophenolate mofetil, also known as MMF or CellCept, is a prodrug of mycophenolic acid, and classified as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). This drug is an immunosuppressant combined with drugs such as and corticosteroids to prevent organ rejection after hepatic, renal, and cardiac transplants. It is marketed by Roche Pharmaceuticals and was granted FDA approval for the prophylaxis of transplant rejection in 1995. In addition to the above uses, mycophenolate mofetil has also been studied for the treatment of nephritis and other complications of autoimmune diseases. Unlike another immunosuppressant class, the calcineurin inhibitors, MMF generally does not cause nephrotoxicity or fibrosis.
Previously, mycophenolic acid (MPA) was administered to individuals with autoimmune diseases beginning in the 1970s, but was discontinued due to gastrointestinal effects and concerns over carcinogenicity. The new semi-synthetic 2-morpholinoethyl ester of MPA was synthesized to avoid the gastrointestinal effects associated with the administration of MPA. It demonstrates an increased bioavailability, a higher efficacy, and reduced gastrointestinal effects when compared to MPA.
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| CAS Number: |
128794-94-5
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| Molecular Weight: |
433.4947
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| DrugBank Indication: |
Mycophenolate mofetil is indicated for the prophylaxis of organ rejection in patients undergoing allogeneic renal, hepatic, or cardiac transplants. It should be used with cyclosporine and corticosteroids. Mycophenolate mofetil may also be used off-label as a second-line treatment for autoimmune hepatitis that has not responded adequately to first-line therapy. Other off-label uses of this drug include lupus-associated nephritis and dermatitis in children.
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| DrugBank Pharmacology: |
Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection. The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection.
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| DrugBank MoA: |
The active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies. Lymphocyte and monocyte adhesion to endothelial cells of blood vessels that normally part of inflammation is prevented via the glycosylation of cell adhesion molecules by MPA. MPA inhibits de novo purine biosynthesis (that promotes immune cell proliferation) by inhibiting inosine 5’-monophosphate dehydrogenase enzyme (IMPDH), with a preferential inhibition of IMPDH II. IMPDH normally transforms inosine monophosphate (IMP) to xanthine monophosphate (XMP), a metabolite contributing to the production of guanosine triphosphate (GTP). GTP is an important molecule for the synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein. As a result of the above cascade of effects, mycophenolate mofetil reduces de-novo production of guanosine nucleotides, interfering with the synthesis of DNA, RNA, and protein required for immune cell production. Further contributing to the above anti-inflammatory effects, MMF depletes tetrahydrobiopterin, causing the decreased function of inducible nitric oxide synthase enzyme, in turn decreasing the production of peroxynitrite, a molecule that promotes inflammation.
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| Targets: |
Inosine-5'-monophosphate dehydrogenase 1 inhibitor&inducer; Inosine-5'-monophosphate dehydrogenase 2 inhibitor; 6-pyruvoyl tetrahydrobiopterin synthase inhibitor
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| Inclusion Criteria: |
Therapeutic strategy associated
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