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
Identifiers & Physical Properties
| CAS No. | 341031-54-7 |
|---|---|
| Molecular formula | C26H33FN4O7 |
| Average molar mass | 532.6 g/mol |
| Monoisotopic mass | 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 |
Chemical & Physical Properties
| Topological polar surface area | 172 |
|---|---|
| Hydrogen bond donors | 6 |
| Hydrogen bond acceptors | 9 |
| Rotatable bonds | 10 |
| Heavy atoms | 38 |
| Formal charge | 0 |
| Complexity | 765 |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Melting point | 189-191°C |
| Storage conditions | room temp |
| Solubility | DMSO: >10mg/mL |
| Physical state | powder |
| pKa (acidity coefficient) | 8.95 |
| Color | Orange |
| Stability | 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 DataBase Reference | 341031-54-7(CAS DataBase Reference) |
| NCI Dictionary of Cancer Terms | SU011248sunitinib malate |
| FDA UNII | LVX8N1UT73 |
| NCI Drug Dictionary | sunitinib malate |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| GHS pictogram | GHS08 |
| Signal word | Danger |
| GHS hazard statements | H360-H372 |
| GHS precautionary statements | P201-P308+P313 |
| Hazard symbols | T |
| Risk statements (R) | 61-2-48/25-36/37-22-53 |
| Safety statements (S) | 53-22-36/37-24/25 |
| UN transport number | UN3077 |
| Water hazard class (WGK) | 2 |
| Hazard class | 9Repr. 1BSTOT RE 1 Oral |
| Customs code | 29337900 |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Limited quantities | 5.0 kg (11 lbs) (solid) |
| Excepted quantities | Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L) |
Safety & Regulations
| GHS classification | 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 |
| Water hazard class (WGK) | 2 |
| UN transport number | UN3077 |
| Customs code | 29337900 |
| Risk statements (R) | 61-2-48/25-36/37-22-53 |
| Signal word | Danger |
| GHS pictogram | GHS08 |
| Hazard symbols | T |
| Safety statements (S) | 53-22-36/37-24/25 |
| Hazard class | 9Repr. 1BSTOT RE 1 Oral |
| Storage class | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| GHS hazard statements | H360-H372 |
| Limited quantities | 5.0 kg (11 lbs) (solid) |
| Excepted quantities | Max Inner Pack (30g or 30ml) and Max Outer Pack (1Kg or 1L) |
| GHS precautionary statements | P201-P308+P313 |
Applications & Uses
Uses
Anti-cancer drugs
Description
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.
Uses
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.
Uses
Sunitinib Malate 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
Uses
A multi-kinase inhibitor targeting several receptor tyrosine kinases (RTK). Antineoplastic.
General Description
Sunitinib is available in 12.5-, 25-, and 50-mg capsules fororal administration for the treatment of advanced RCC andGIST upon the failure of imatinib. The agent is a multikinaseinhibitor and has been shown to inhibit PDGF-R,VEGF-R, Kit, RET, and the colony-stimulating factor receptor(CSR-1R). The result of this spectrum of activity isa slowing of tumor progression and inhibition of angiogenesisboth of which are useful in the highly vascularizedcancers, RCC and GIST. The median TTP (time to tumorprogression) was 27.3 weeks for sunitinib and 6.4 weeks with a median time of 24.1 weeks for sunitinib and 6 weeksfor placebo. The agent is well absorbed upon oral administration,and both the parent and major metabolite are highly(90%–95%) protein bound. Metabolism is mediated primarilyby CYP3A4 to give the N-desethyl derivative, which isthe major metabolite (23%–37%), equally active with theparent and undergoes further metabolism by CYP3A4. Theterminal elimination half-life for the parent and N-desethylderivative are 40 to 60 hours and 80 to 110 hours, respectively.Elimination occurs primarily via the feces. Commonadverse effects of sunitinib include fatigue, diarrhea, yellowskin discoloration, anorexia, nausea, and mucositis.Mild myelosuppression has been reported in patients withGIST including neutropenia, lymphopenia, thrombocytopenia,and anemia. There have been reports of cardiotoxicityincluding decreases in left ventricular ejectionfraction, which occurred in 11% of patients during a GISTstudy.