128794-94-5 Usage
Description
Mycophenolate mofetil, also known as CellCept, is a white powder prodrug of mycophenolic acid (MPA), a fermentation product of several Penicillium species. Launched in 1995 in the U.S.A., it is an immunosuppressant with improved oral absorption and bioavailability. MPA is a selective, reversible, non-competitive inhibitor of inosinate dehydrogenase and guanylate synthetase, inhibiting the de novo pathway of purine biosynthesis. Mycophenolate mofetil has potent antiproliferative effects on T and B lymphocytes, making it superior to other immunosuppressants due to its unique mechanism of action and excellent safety profile for long-term use.
Uses
Used in Transplantation:
Mycophenolate mofetil is used as an immunosuppressant for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants. It should be used concomitantly with cyclosporine and corticosteroids to ensure effective prevention of organ rejection.
Used in Autoimmune Diseases:
Mycophenolate mofetil is being investigated clinically for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis, and preventing coronary artery restenosis. Its unique mechanism of action and safety profile make it a promising candidate for managing these conditions.
Used in Embryo Development:
Mycophenolate mofetil has been used to treat wild-type embryos for inhibiting nucleotide synthesis, which can have potential applications in the field of embryonic development and research.
Originator
Roche (Switzerland)
Indications
Mycophenolate mofetil (MMF, CellCept) is an ester
prodrug of mycophenolic acid (MPA), a Penicillium-derived
immunosuppressive agent that
blocks de novo purine synthesis by noncompetitively inhibiting
the enzyme inosine monophosphate dehydrogenase.
MPA preferentially suppresses the proliferation
of cells, such as T and B lymphocytes, that lack the
purine salvage pathway and must synthesize de novo the guanosine nucleotides required for DNA and RNA
synthesis.MPA has been used for decades as a systemic
treatment for moderate to severe psoriasis. MMF was
developed to increase the bioavailability of MPA.
Biochem/physiol Actions
Mycophenolate mofetil is a prodrug of mycophenolic acid (Cat. # M5255) that is cleaved by nonspecific esterases in vivo to produce the parent compound. Mycophenolic acid blocks inosine monophosphate dehydrogenase and is a potent immunosuppresive agent.
Mechanism of action
the guanosine nucleotides required for DNA and RNA
synthesis.MPA has been used for decades as a systemic
treatment for moderate to severe psoriasis. MMF was
developed to increase the bioavailability of MPA.
Clinical Use
MMF is indicated for the prophylaxis of organ rejection
in patients receiving renal, hepatic, and cardiac
transplants; it is often used in combination with other
immunosuppressive agents for this indication. In dermatology,
MMF is particularly useful as monotherapy, or as
a steroid-sparing agent, for treatment of autoimmune
blistering diseases (bullous pemphigoid and pemphigus).
It may also be useful for the treatment of inflammatory
skin diseases mediated by neutrophilic infiltration,
such as pyoderma gangrenosum, and psoriasis.
Side effects
Adverse effects produced by MMF most
commonly include nausea, abdominal cramps, diarrhea,
and possibly an increased incidence of viral and bacterial
infections. Whether MMF may be associated with
an increased long-term risk of lymphoma or other malignancies
is controversial; however, any such risk is
likely to be lower in patients treated for skin disease
with MMF monotherapy than in transplant patients
treated with combination immunosuppressive therapy.
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Antivirals: higher concentrations of both
mycophenolate and aciclovir or ganciclovir when the
two are prescribed concomitantly.
Antacids: absorption of mycophenolate decreased in
presence of magnesium and aluminium salts.
Antibacterials: bioavailability of mycophenolate
possibly reduced by metronidazole and norfloxacin;
concentration of active metabolite reduced by
rifampicin.
Colestyramine: 40% reduction in oral bioavailability
of mycophenolate.
Ciclosporin: some studies show that ciclosporin
decreases plasma MPA AUC levels; other studies
show increases - no dose change required.
Iron preparations: may significantly reduce
absorption of mycophenolate.
Sevelamer: reduced levels of mycophenolate.
Tacrolimus: increases MPA concentrations- no dose
change required but monitor closely.
See 'Other information'
Metabolism
Mycophenolate undergoes presystemic metabolism
in the liver to active mycophenolic acid (MPA). MPA
undergoes enterohepatic recirculation and secondary
increases in plasma MPA concentrations are seen; these
have been reported at between 6-12 hours after a dose of
mycophenolate mofetil, and at between 6-8 hours after
a dose of mycophenolate sodium. MPA is metabolised
by glucuronidation to the inactive mycophenolic acid
glucuronide.
The majority of a dose of mycophenolate is excreted in
the urine as this glucuronide, with negligible amounts of
MPA; about 6% of a dose is recovered in faeces.
References
1) Allison and Eugui (1996), Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF); Clin. Transplant., 10 77
2) Jonsson et al. (2002), Mycophenolic acid inhibits inosine 5′-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages; Cell. Immunol., 216 93
3) Allison et al. (1993), Mechanisms of action of mycophenolic acid; Ann. NY Acad. Sci., 696 63
4) Quemeneur et al. (2002), Mycophenolic acid inhibits IL-2-dependent T cell proliferation, but not IL-2-dependent survival and sensitization to apoptosis; J. Immunol., 169 2747
5) Ebrahimi et al. (2012) Time dependent neuroprotection of mycophenolate mofetil; effects on temporal dynamics in glial proliferation, apoptosis, and scar formation; J. Neuroinflammation, 9 89
Check Digit Verification of cas no
The CAS Registry Mumber 128794-94-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,8,7,9 and 4 respectively; the second part has 2 digits, 9 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 128794-94:
(8*1)+(7*2)+(6*8)+(5*7)+(4*9)+(3*4)+(2*9)+(1*4)=175
175 % 10 = 5
So 128794-94-5 is a valid CAS Registry Number.
InChI:InChI=1/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3
128794-94-5Relevant articles and documents
MYCOPHENOLIC ACID RECYCLING IN A METHOD FOR THE PREPARATION OF MYCOPHENOLATE MOFETIL
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Page/Page column 8-12, (2009/03/07)
The present invention provides a method for the preparation of mycophenolate mofetil wherein mycophenoiic acid is mixed with 2-morpholinoethanol in a water-immiscible solvent, followed by addition of water and adjustment of the pH to a value ranging from 0 to 3 or ranging from 7 to 10 and separating the organic and aqueous phases. Mycophenolate mofetil is isolated from the relevant phase and the mycophenoiic acid present in the alternate phase is re-used in a conversion of mycophenoiic acid to mycophenolate mofetil.
