HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Capmatinib
INC280 · INCB28060 · INC28060 · 2-Fluoro-N-Methyl-4-(7-quinolin-6-ylMethyl-iMidazo[1,2-b][1,2,4] triazin-2-yl)-benzaMide · NC280 · CS-192 · INCB028060 · NVP-INC280
Identifikatoren & physikalische Daten
| CAS No. | 1029712-80-8 |
|---|---|
| Summenformel | C23H17FN6O |
| Durchschnittliche Molmasse | 412,4 g/mol |
| Monoisotopische Masse | 412,14478738 g/mol |
| SMILES | CNC(=O)c1ccc(-c2cnc3ncc(Cc4ccc5ncccc5c4)n3n2)cc1F |
| InChIKey | LIOLIMKSCNQPLV-UHFFFAOYSA-N |
| PubChem CID | 25145656 |
| ChEMBL | CHEMBL3188267 |
| ChEBI | CHEBI:231693 |
| EC No. | 813-241-9 |
| DTXSID | DTXSID90145595 |
Chemische & physikalische Eigenschaften
| XLogP | 2,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 85,1 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 6 |
| Frei drehbare Bindungen | 4 |
| Schwere Atome | 31 |
| Formalladung | 0 |
| Komplexität | 637 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| Human Drugs | Breast FeedingLactationMilk, HumanEnzyme InhibitorsProtein Kinase InhibitorsSignal Transduction InhibitorsEMA approved medicines: Human medicine |
| Schmelzpunkt | >250°C (dec.) |
| Dichte | 1.40 |
| Dampfdruck | 0-0Pa at 20-25℃ |
| Lagerbedingungen | -20°C Freezer, Under inert atmosphere |
| Löslichkeit | DMSO (Slightly), Methanol (Slightly) |
| pKa (Säurekonstante) | 13.82±0.46(Predicted) |
| Aggregatzustand | Solid |
| Farbe | Pale Yellow to Light Yellow |
| InChI | InChI=1S/C23H17FN6O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20/h2-9,11-13H,10H2,1H3,(H,25,31) |
| InChIKey | LIOLIMKSCNQPLV-UHFFFAOYSA-N |
| SMILES | C(NC)(=O)C1=CC=C(C2=NN3C(CC4=CC=C5C(=C4)C=CC=N5)=CN=C3N=C2)C=C1F |
| LogP (Verteilungskoeffizient) | 1.6-2.2 at 35℃ and pH7-9 |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P260, P264, P270, P273, P280, P301+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 8 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 19-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/34794 |
| Hazard Classes and Categories | Acute Tox. 3 (100%) |
| Hepatotoxicity | In the prelicensure clinical trials of capmatinib in patients with solid tumors harboring MET mutations, liver test abnormalities were frequent although usually self-limited and mild. Some degree of ALT elevations arose in 39% of capmatinib treated patients and were above 5 times the upper limit of normal (ULN) in 7%. In these trials that enrolled 373 patients, capmatinib was discontinued early due to increased AST or ALT in only 1% of patients. The liver test abnormalities had a median onset of 2 months after initiation of therapy. While serum aminotransferase elevations were occasionally quite high (5 to 20 times upper limit of normal), there were no accompanying elevations in serum bilirubin and no patient developed clinically apparent liver injury with jaundice. The product label for capmatinib recommends monitoring for routine liver tests before, at 2-week intervals during the first 3 months of therapy, and monthly thereafter as clinically indicated. However, since its approval and more wide-spread clinical use, there have been several reports of acute liver injury with jaundice in patients receiving capmatinib. The onset is after 6 to 8 weeks, and the clinical pattern is hepatocellular with features resembling severe acute viral hepatitis. Immune allergic and autoimmune features are not common, and recovery occurs typically within 2 to 3 months, but at least one fatal incident has been reported. Strikingly, most cases have occurred shortly after previous chemotherapy with a checkpoint inhibitor (within 2 to 4 months of the last dose). A similar frequent occurrence of liver injury following recent use of checkpoint inhibitors has been reported with other kinase inhibitors (sotorasib, crizotinib, osimertinib). These findings suggest that capmatinib not be started within 4 months of the last dose of a checkpoint inhibitor. |
| Effects During Pregnancy and Lactation |
Anwendungen & Verwendung
Beschreibung
Capmatinib is a competitive inhibitor with very potent and selective activity against MET compared to other kinases.
Verwenden
2-Fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide is used in the preparation of a combination formulation with allosteric SHP2 inhibitor TNO155. Used in treatment of non-small cell lung cancer with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).