Disease relevance of mycophenolic acid

• Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo [1].
• Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations [1].
• Mycophenolic Acid Inhibits Hepatitis C Virus Replication and Acts in Synergy With Cyclosporin A and Interferon-alpha [2].
• There were no significant associations between MPA pharmacokinetics and acute graft-versus-host disease (GVHD) or relapse [3].
• Biological effects of inhibition of guanine nucleotide synthesis by mycophenolic acid in cultured neuroblastoma cells [4].

Psychiatry related information on mycophenolic acid

• The toxicity induced by the conditioning therapy seems to negatively influence the pharmacokinetic behavior of MMF, MPA and MPAG [5].

High impact information on mycophenolic acid

• The structure of inosine-5'-monophosphate dehydrogenase (IMPDH) in complex with IMP and mycophenolic acid (MPA) has been determined by X-ray diffraction [6].
• Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes) [1].
• The drugs 6-azauracil and mycophenolic acid reduce both the elongation rate and processivity, and this processivity defect is aggravated by mutations in Spt4, TFIIS, and CTDK-1 [7].
• Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone [8].
• In one transfectant clone, integration of these sequences into human chromosome 17 was demonstrated by the construction of human-mouse somatic cell hybrids, selected for by growth in medium containing mycophenolic acid and xanthine [9].

Chemical compound and disease context of mycophenolic acid

• However, guanosine was as effective as deoxyguanosine at preventing mycophenolic acid toxicity although deoxyguanosine was more effective at elevating dGTP levels [10].
• Moreover, in hypoxanthine-guanine phosphoribosyltransferase-deficient mutants of S-49 (6MPR-3-3) deoxyguanosine was unable to prevent mycophenolic acid toxicity or to re-establish normal DNA synthesis, although it returned cellular dGTP but not GTP levels to normal [10].
• Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses [11].
• The effects of the inhibitors of IMP dehydrogenase, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) and mycophenolic acid, on the synthesis of cellular glycoproteins were evaluated in Sarcoma 180 cells [12].
• It is noteworthy that systemic MPA exposure is higher with EC mycophenolate sodium than with mycophenolate mofetil, without increased gastrointestinal toxicity [13].

Biological context of mycophenolic acid

• Clones containing the hybrid plasmid were selected by their resistance to mycophenolic acid [14].
• Its activity is correlated with cell growth, and it is the target of a number of proven and experimental drug therapies including mycophenolic acid (MPA) [15].
• MPA pharmacokinetics were determined on days 7 and 21 [3].
• We have examined the induction of apoptosis by mycophenolic acid (MPA), a specific IMPDH inhibitor, in interleukin-3 (IL-3)-dependent murine hematopoietic cell lines [16].
• Sixteen patients with a total MPA Css less than 3 microg/mL had low (< 50%) donor T-cell chimerism (P = .03), and 6 patients with MPA Css less than 2.5 microg/mL had graft rejection [3].

Anatomical context of mycophenolic acid

• Large unilamellar liposomes, coated with protein A and encapsulating the gene that confers resistance to mycophenolic acid, were used as a model system to demonstrate gene transfer into specific lymphoid cells [17].
• Mycophenolic acid treatment of mouse long-term bone marrow cultures depletes them of all assayable hematopoietic precursors [18].
• We now show that these mycophenolic acid-treated stromal cell cultures contain cells capable of hematopoietic differentiation without the addition of new progenitors [18].
• In contrast to the pattern of increased IMPDH expression observed in the mycophenolic acid-treated cells, treatment of HL-60 cells with two other inducers of differentiation, namely retinoic acid and phorbol 12-myristate 13-acetate, resulted in stable or decreased levels of cellular IMPDH mRNA and protein [19].
• Human liver DNA was transfected into CHO cells (mex-) along with pSV2gpt and colonies were selected first for resistance to mycophenolic acid and then to chloroethylnitrosourea [20].

Associations of mycophenolic acid with other chemical compounds

• Treatment of cells with an inhibitor of guanine nucleotide biosynthesis, mycophenolic acid, enhanced detection of GFAP by indirect immunofluorescence microscopy [21].
• To establish a system to study differentiation therapy drugs, we used the androgen-independent human prostate PC-3 tumor cell line as a target and mycophenolic acid (MPA), tiazofurin, or ribavirin, which are inhibitors of IMP dehydrogenase, as inducers [22].
• Mimosine, like MPA, also increased p21(Waf1/Cip1), promoted apoptosis and simultaneously increased the activity of caspases [23].
• Moreover, this additional transcript was not detected during induction of HL-60 cells by dimethyl sulfoxide, tumor necrosis factor, and retinal, but was induced by another IMP dehydrogenase inhibitor, mycophenolic acid [24].
• A prototypic uncompetitive inhibitor of IMPDH, mycophenolic acid (MPA), is the active form of mycophenolate mofeteil (CellCept), a widely used immunosuppressive drug [25].

Gene context of mycophenolic acid

• The immunosuppressive drug mycophenolic acid (MPA) is a potent and specific inhibitor of IMP dehydrogenase, the first committed step of GMP synthesis [26].
• We also show that a deletion of RTF1 causes sensitivity to 6-azauracil and mycophenolic acid, phenotypes correlated with a transcription elongation defect [27].
• Although Imd2 is 92% identical to Imd3, it is the only S. cerevisiae IMPDH that is resistant to mycophenolic acid in vitro and is the only one of the four that supports drug-resistant growth [28].
• The human UDP glucuronosyltransferase, UGT1A10, glucuronidates mycophenolic acid [29].
• The identities of the UDP glucuronosyltransferase forms that are mainly responsible for the glucuronidation of mycophenolic acid in the liver and kidney remain unknown; however, UGT1A9 may be important in this respect as the cDNA-expressed enzyme has some capacity to glucuronidate mycophenolic acid [30].

Analytical, diagnostic and therapeutic context of mycophenolic acid

• Southern blotting with the probe indicated an amplification of the IMPDH gene in the mycophenolic acid-resistant cells [31].
• Western blot (immunoblot) analysis with an IMPDH antiserum revealed a 14- to 27-fold increase in the amount of enzyme in the mycophenolic acid-resistant cells [31].
• In cell culture, C. albicans is sensitive to mycophenolic acid (MPA) and mizoribine, both natural product inhibitors of IMP dehydrogenase (IMPDH) [32].
• Explaining variability in mycophenolic acid exposure to optimize mycophenolate mofetil dosing: a population pharmacokinetic meta-analysis of mycophenolic acid in renal transplant recipients [33].
• Mycophenolic acid (MPA) blood levels were measured by both HPLC and EMIT, and MPA-glucuronide was determined by HPLC [34].

References