Osimertinib
Mereletinib · ADZ9291 · N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide · ZAD9291 · AZD929/Osimertinib · Osimertinib Intermediate 4 · N-(2-{[2-(Dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin · osim
Identifikatoren & physikalische Daten
| CAS No. | 1421373-65-0 |
|---|---|
| Summenformel | C28H33N7O2 |
| Durchschnittliche Molmasse | 499,6 g/mol |
| Monoisotopische Masse | 499,2695733 g/mol |
| SMILES | C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C |
| InChIKey | DUYJMQONPNNFPI-UHFFFAOYSA-N |
| PubChem CID | 71496458 |
| ChEMBL | CHEMBL3353410 |
| ChEBI | CHEBI:90943 |
| EC No. | 108-168-8 |
| DTXSID | DTXSID501025961 |
Chemische & physikalische Eigenschaften
| XLogP | 3,7 |
|---|---|
| Polarare Oberfläche (TPSA) | 87,6 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 7 |
| Frei drehbare Bindungen | 10 |
| Schwere Atome | 37 |
| Formalladung | 0 |
| Komplexität | 752 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| Human Drugs | Breast FeedingLactationAntineoplastic AgentsEnzyme InhibitorsProtein Kinase InhibitorsSignal Transduction InhibitorsEMA approved medicines: Human medicine |
| Schmelzpunkt | >188oC (dec.) |
| Dichte | 1.19±0.1 g/cm3(Predicted) |
| Lagerbedingungen | Hygroscopic, -20°C Freezer, Under inert atmosphere |
| Löslichkeit | DMSO (Slightly, Heated), Methanol (Slightly, Heated) |
| pKa (Säurekonstante) | 12.68±0.70(Predicted) |
| Aggregatzustand | Solid |
| Farbe | Pale Yellow to Beige |
| InChIKey | DUYJMQONPNNFPI-UHFFFAOYSA-N |
| SMILES | CN1C2=CC=CC=C2C(C2C=CN=C(NC3C=C(NC(=O)C=C)C(N(C)CCN(C)C)=CC=3OC)N=2)=C1 |
| CAS Datenbank | 1421373-65-0 |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P318, P319, P321, P330, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (50%) |
| Hepatotoxicity | Elevations in serum aminotransferase levels are uncommon during osimertinib therapy occurring in 4% to 5% of patients and rising above 5 times the upper limit of the normal range in only 1% or less. In preregistration trials, there was a single incidence of clinically apparent liver injury attributed to osimertinib therapy, but the clinical features and relatedness to therapy were not defined. Since its approval and more widespread use, there have been no published cases of liver injury due to osimertinib. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Zollcode | 29339900 |
Anwendungen & Verwendung
Beschreibung
AZD-9291 (Mesylate), also known as Osimertinib, belongs to a third-generation EGFR (epidermal growth factor receptor) inhibitor. It can be used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in case when the cancer cells carry specific mutations (such as T790M) in the epidermal growth factor receptor. It takes effect through directly binding to the certain mutant forms of EGFR (T790M, L858R, and exon 19 deletions) that are frequently found in NSCLC, further causing poor prognosis for late-stage disease. Since it spares wild type EGFR during therapy, it has only limited toxicity.
Verwenden
AZD 9291 is an irreversible inhibitor of epidermal growth factor receptor (EGFR) sensitizing and T790M resistance mutations (IC50s = 15-17 nM) while sparing the wild-type form of the receptor (IC50 = 480 nM). It binds the related IGF1R and hERG receptors with significantly reduced potency (IC50s = 2.9 and 16.2 μM, respectively). AZD 9291 has been shown to inhibit tumor growth in a xenograft mouse model at oral doses of 5-10 mg/kg and has been tested clinically in patients with advanced EGFR mutant non-small-cell lung cancer.[Cayman Chemical]