Mycophenolinsäure
Mycophenolic · (E)-6-(4-hydroxy-6-Methoxy-7-Methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-Methylhex-4-enoic acid · melbex · nsc-129185 · MycophenoL · Mycophenolate Mofetil EP Impurity F · 68618 · lilly-68618
Identifikatoren & physikalische Daten
| CAS No. | 24280-93-1 |
|---|---|
| Summenformel | C17H20O6 |
| Durchschnittliche Molmasse | 320,3 g/mol |
| Monoisotopische Masse | 320,12598836 g/mol |
| SMILES | COc1c(C)c2c(c(O)c1C/C=C(\C)CCC(=O)O)C(=O)OC2 |
| InChIKey | HPNSFSBZBAHARI-RUDMXATFSA-N |
| PubChem CID | 446541 |
| ChEMBL | CHEMBL866 |
| ChEBI | CHEBI:168396 |
| EC No. | 246-119-3 |
| DTXSID | DTXSID4041070 |
| Lokaler Name | Mycophenolinsäure |
Chemische & physikalische Eigenschaften
| XLogP | 3,2 |
|---|---|
| Polarare Oberfläche (TPSA) | 93,1 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 6 |
| Frei drehbare Bindungen | 6 |
| Schwere Atome | 23 |
| Formalladung | 0 |
| Komplexität | 485 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Metabolite of Mycophenolate mofetilPharmaceuticals -> Antibiotics |
| LogP (Verteilungskoeffizient) | 2.82.76 |
| Löslichkeit | Insoluble3.55e-02 g/Lmethanol: 50 mg/mL, clear, colorless to faintly yellow13mg/L(25 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanImmunosuppressive Agents |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| Schmelzpunkt | 141°C141 °C |
| Physical Description | Solid |
| Collision Cross Section | 165.4 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]176 Ų [M+NH4]+ [CCS Type: TWMethod: calibrated with polyalanine] |
| Siedepunkt | 419.24°C (rough estimate) |
| Dichte | 1.2300 (rough estimate) |
| Dampfdruck | 0Pa at 22℃ |
| Brechungsindex | 1.5200 (estimate) |
| Flammpunkt | 2℃ |
| Lagerbedingungen | Sealed in dry,Store in freezer, under -20°C |
| Aggregatzustand | powder |
| pKa (Säurekonstante) | 4.5(at 25℃) |
| Farbe | white to white with yellow cast |
| Merck | 14,6327 |
| BRN | 1295848 |
| BCS Class | 2 |
| Stabilität | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| Hauptanwendungen | clinical testing |
| InChI | 1S/C17H20O6/c1-9(5-7-13(18)19)4-6-11-15(20)14-12(8-23-17(14)21)10(2)16(11)22-3/h4,20H,5-8H2,1-3H3,(H,18,19)/b9-4+ |
| InChIKey | HPNSFSBZBAHARI-RUDMXATFSA-N |
| SMILES | COc1c(C)c2COC(=O)c2c(O)c1C\C=C(/C)CCC(O)=O |
| LogP (Verteilungskoeffizient) | -1.83-2.28 at 25℃ and pH5-9 |
| CAS Datenbank | 24280-93-1(CAS DataBase Reference) |
| EPA chemische Informationen | 4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (4E)- (24280-93-1) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 89 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 07-09-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/159774-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (4E)-: Does not have an individual approval but may be used under an appropriate group standard |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Expositionspfade | Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95% |
| Toxizitätsübersicht | Mycophenolic acid is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, mycophenolic acid has potent cytostatic effects on lymphocytes. Mycophenolic acid inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes. Mycophenolic acid prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. |
| Signs and Symptoms | Possible signs and symptoms of acute overdose could include the following: hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
Anwendungen & Verwendung
Beschreibung
Mycophenolic acid is an immunosuppresive microbial metabolite that has been found in P. brevicompactum. It is also an active metabolite of mycophenolate mofetil that is formed via carboxylesterase 1 (CES1) and CES2. Mycophenolic acid is an inhibitor of IMP dehydrogenase (IMPDH) type I and type II (IC50s = 32 and 11 nM, respectively, in cell-free assays) and inhibits DNA synthesis in L strain mouse fibroblasts when used at concentrations ranging from 0.1 to 10 μg/ml. It is active against several strains of C. albicans, C. parakrusei, C. tropicalis, and C. neoformans (MICs = 3.9-31.25 μg/ml), as well as various strains of S. aureus (MICs = 31.25-125 μg/ml). Mycophenolic acid (150 mg/kg) reduces splenomegaly in a mouse model of Friend virus-induced leukemia. It decreases the number of hemolytic plaque forming cells isolated from the spleen of mice immunized with sheep red blood cells (RBCs) when administered at doses ranging from 60 to 240 mg/kg. Formulations containing mycophenolic acid have been used as immunosuppressive agents in the prevention of organ transplant rejection.
Verwenden
Mycophenolic acid is a common Penicillium metabolite first reported in the 1930s as a possible mycotoxin. Re-investigation showed mycophenolic acid to display broad antitumour, antiviral, antifungal and antiprotozoan activities. Its potent immunosuppressant activity led to its commercial development to prevent kidney transplant rejection. Mycophenolic acid acts by inhibiting inosine monophosphate dehydrogenase, controlling the rate of de novo purine synthesis in proliferating B and T lymphocytes.