りんご酸スニチニブ
りんご酸スニチニブ · SUNITINIB MALATE (SUTENT) · スニチニブリンゴ酸塩 · スニチニブリンゴ酸塩 (JAN) · N-[2-(ジエチルアミノ)エチル]-5-[(Z)-(5-フルオロ-2-オキソ-1,2-ジヒドロ-3H-インドール-3-イリデン)メチル]-2,4-ジメチル-1H-ピロール-3-カルボアミド・(2S)-2-ヒドロキシコハク酸 · スニチニブL-マラート · N-[2-(ジエチルアミノ)エチル]-5-[(Z)-[5-フルオロ-2-オキソ-1H-インドール-3(2H)-イリデン]メチル]-2,4-ジメチル-1H-ピロール-3-カルボアミド・(2S)-2-ヒドロキシブタン二酸 · N-[2-(ジエチルアミノ)エチル]-5-[(Z)-(5-フルオロ-2-オキソ-1,2-ジヒドロ-3H-インドール-3-イリデン)メチル]-2,4-ジメチルピロール-3-カルボキサミド=(2S)-2-ヒドロキシコハク酸塩
識別子と物理属性
| CAS No. | 341031-54-7 |
|---|---|
| 分子式 | C26H33FN4O7 |
| 平均分子量 | 532.6 g/mol |
| 単同位体質量 | 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 |
| 現地名 | りんご酸スニチニブ |
化学・物理的性質
| 極性表面積 | 172 |
|---|---|
| 水素結合供与体数 | 6 |
| 水素結合受容体数 | 9 |
| 回転可能結合数 | 10 |
| 重原子数 | 38 |
| 形式電荷 | 0 |
| 複雑度 | 765 |
| Human Drugs | FDA approved drugs -> Active ingredient |
| 融点 | 189-191°C |
| 貯蔵条件 | room temp |
| 溶解度 | DMSO：>10mg/mL |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 8.95 |
| 色 | オレンジ |
| 安定性 | 購入日から2年間安定です。この DMSO 溶液は、-20°C で 3 か月間保存できます。 |
| 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 データベース | 341031-54-7(CAS DataBase Reference) |
化学的特性
Yellow Solid
安全性と法規制
| GHS 分類 | 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 |
| 水環境危害等級（WGK） | 2 |
| 輸送番号（UN） | UN3077 |
| 税関コード | 29337900 |
| 危険文句（R） | 61-2-48/25-36/37-22-53 |
| 危険表示 | T |
| 安全措置（S） | 53-22-36/37-24/25 |
| 危険等級 | 9Repr. 1BSTOT RE 1 Oral |
| 貯蔵分類 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
用途
用途
強力な VEGFR, PDGFRβ 及び KIT の阻害剤です（Ki=2 nM（VEGFR-1），9 nM（VEGFR-2）， 17 nM（VEGFR-3），8 nM（PDGFRβ），4 nM（KIT））。
用途
強力なVEGFR, PDGFRβ及びKITの阻害剤です（Ki=2 nmol/l（VEGFR-1），9 nmol/l（VEGFR-2）， 17 nmol/l（VEGFR-3），8 nmol/l（PDGFRβ），4 nmol/l（KIT））。
説明
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.
使用
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.
一般的な説明
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.