Nilotinib
Tasigna · Nilotinib-d6 · AMN 107 · 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4 -pyridin-3-ylpyrimidin-2-yl)amino]benzamide · CS-307 · Nilotinib · Nilotinibr · Nilotinib &aMp
Identifikatoren & physikalische Daten
| CAS No. | 641571-10-0 |
|---|---|
| Summenformel | C28H22F3N7O |
| Durchschnittliche Molmasse | 529,5 g/mol |
| Monoisotopische Masse | 529,18379284 g/mol |
| SMILES | Cc1cn(-c2cc(NC(=O)c3ccc(C)c(Nc4nccc(-c5cccnc5)n4)c3)cc(C(F)(F)F)c2)cn1 |
| InChIKey | HHZIURLSWUIHRB-UHFFFAOYSA-N |
| PubChem CID | 644241 |
| ChEMBL | CHEMBL255863 |
| ChEBI | CHEBI:52172 |
| EC No. | 700-544-5 |
| DTXSID | DTXSID5042663 |
Chemische & physikalische Eigenschaften
| XLogP | 4,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 97,6 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 9 |
| Frei drehbare Bindungen | 6 |
| Schwere Atome | 39 |
| Formalladung | 0 |
| Komplexität | 817 |
| Color/Form | White to slightly yellowish to slightly greenish yellow powder |
| Löslichkeit | The solubility ... in aqueous solutions decreases with increasing pH2.01e-03 g/LSoluble in DMSO (up to 50 mg/ml) |
| Physical Description | Solid |
| Dissociation Constants | pKa1 = 2.1pKa2 = 5.4 |
| Other Experimental Properties | A monohydrate monohydrochloride |
| Schmelzpunkt | 231-233 °C |
| Dichte | 1.36 |
| Lagerbedingungen | -20°C Freezer |
| Aggregatzustand | Beige powder. |
| Farbe | Off-white |
| Stabilität | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| InChIKey | HHZIURLSWUIHRB-UHFFFAOYSA-N |
| SMILES | N1(C=C(C)N=C1)C1C=C(C=C(C=1)NC(=O)C1C=CC(C)=C(NC2=NC=CC(C3=CC=CN=C3)=N2)C=1)C(F)(F)F |
| CAS Datenbank | 641571-10-0(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH361 (69.2%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]H361fd (46.2%): Suspected of damaging fertilitySuspected of damaging the unborn child [Warning Reproductive toxicity]H372 (15.4%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]H373 (76.9%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]H400 (69.2%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]H410 (69.2%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]H413 (23.1%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]P203, P260, P264, P270, P273, P280, P318, P319, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 13 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 21-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/34814 |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including nilotinib hydrochloride monohydrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Nilotinib hydrochloride monohydrate/ |
| Hazard Classes and Categories | Repr. 2 (69.2%)STOT RE 1 (15.4%)STOT RE 2 (76.9%)Aquatic Acute 1 (69.2%)Aquatic Chronic 1 (69.2%)Aquatic Chronic 4 (23.1%) |
Anwendungen & Verwendung
Beschreibung
Chronic myeloid leukemia (CML), a hematological stem-cell disorder, is definitively diagnosed by the detection of the Philadelphia chromosome, a truncated version of chromosome 22 resulting from the reciprocal translocation of chromosomes 9 and 22 induced by a single mutagenic event. The consequence is the juxtaposition of two genes creating a fusion gene BCR-ABL. This gene leads to the translation of a fusion protein with increased tyrosine kinase activity that contributes to the pathogenesis of CML. Targeting the BCR-ABL protein has led to the successful intervention of the disease. Now established as first-line therapy for CML, imatinib was the first selective tyrosine kinase inhibitor of BCR-ABL. Since imatinib only binds to an inactive conformation of the ABL kinase portion, the conformational restrictions contribute to its selectivity.
Verwenden
Nilotinib, an orally active signal transduction inhibitor that selectively inhibits the tyrosine kinase Bcr-Abl, was discovered and developed by Norvartis and was launched for the treatment of chronic myeloid leukemia (CML) in patients with Philadelphia chromosome-positive (Ph+) disease who are resistant or intolerant to imatinib mesilate. Additional clinical trials are currently underway for the treatment of acute lymphoblastic leukemia (ALL) and gastrointestinal stromal tumors (GISTs).