Sunitinib Malate
N-(2-(Diethylamino)ethyl)-5-((Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (2S)-hydroxybutanedioate · Sunitinib L-malate · (Z)-N-(2-(Diethylamino)ethyl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrr · CS-308 · NSC2677 · SU112248 · NSC 2677 · NSC-2677
Identifikatoren & physikalische Daten
| CAS No. | 341031-54-7 |
|---|---|
| Summenformel | C26H33FN4O7 |
| Durchschnittliche Molmasse | 532,6 g/mol |
| Monoisotopische Masse | 532,23332762 g/mol |
| SMILES | CCN(CC)CCNC(=O)c1c(C)[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c1C.O=C(O)C[C@H](O)C(=O)O |
| InChIKey | LBWFXVZLPYTWQI-IPOVEDGCSA-N |
| PubChem CID | 6456015 |
| ChEMBL | CHEMBL1567 |
| ChEBI | CHEBI:232546 |
| EC No. | 638-825-9 |
| DTXSID | DTXSID4046492 |
Chemische & physikalische Eigenschaften
| Polarare Oberfläche (TPSA) | 172 |
|---|---|
| H-Brücken-Donoren | 6 |
| H-Brücken-Akzeptoren | 9 |
| Frei drehbare Bindungen | 10 |
| Schwere Atome | 38 |
| Formalladung | 0 |
| Komplexität | 765 |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Schmelzpunkt | 189-191°C |
| Lagerbedingungen | room temp |
| Löslichkeit | DMSO: >10mg/mL |
| Aggregatzustand | powder |
| pKa (Säurekonstante) | 8.95 |
| Farbe | Orange |
| Stabilität | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| InChIKey | XGQXULJHBWKUJY-LYIKAWCPSA-N |
| SMILES | [C@@H](O)(C(=O)O)CC(=O)O.C(/C1NC(C)=C(C(=O)NCCN(CC)CC)C=1C)=C1/C(NC2=CC=C(F)C=C/12)=O |&1:0,r| |
| CAS Datenbank | 341031-54-7(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH360 (93.8%): May damage fertility or the unborn child [Danger Reproductive toxicity]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 48 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Repr. 1B (93.8%) |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Sunitinib malatevMost-DILI-concern8Box warningDOI:10.1016/j.drudis.2016.02.015 |
| Wassergefährdungsklasse (WGK) | 2 |
| UN-Transportnummer | UN3077 |
| Zollcode | 29337900 |
| R-Sätze (R) | 61-2-48/25-36/37-22-53 |
| Gefahrensymbole | T |
| Sicherheitshinweise (S) | 53-22-36/37-24/25 |
| Gefahrenklasse | 9Repr. 1BSTOT RE 1 Oral |
| Lagerklasse | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
Anwendungen & Verwendung
Beschreibung
Sunitinib is a small molecule inhibitor of receptor tyrosine kinases, including FLK1 (Ki = 9 nM), PDGFRβ (Ki = 8 nM), and FLT3. It is at least 10-fold selective for FLK1 and PDGFRβ over a variety of tyrosine kinases in a panel, including EGFR, Cdk2, Met, IGFR-1, Abl, and Src. Sunitinib inhibits VEGF-dependent FLK1 and PDGF-dependent PDGFRβ phosphorylation (IC50s = 10 and 10 nM, respectively) as well as phosphorylation of FLT3 and FLT3 carrying the activating internal tandem duplication mutation (FLT3-ITD; IC50s = 250 and 50 nM, respectively). It decreases VEGF- and FGF-induced proliferation of human umbilical vein endothelial cells (HUVECs; IC50s = 30 and 700 nM, respectively) and reduces tumor growth in a variety of mouse xenograft models when administered at doses ranging from 20 to 80 mg/kg per day. Formulations containing sunitinib have been used in the treatment of gastrointestinal stromal tumors and metastatic renal cell carcinoma.
Verwenden
Sunitinib Malate (Sutent, SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit.