| 名稱 | Nintedanib |
| 描述 | Nintedanib (Intedanib) is a triple vascular kinase inhibitor that inhibits VEGFR1, VEGFR2, and VEGFR3 (IC50=34/13/13 nM), FGFR1, FGFR2, and FGFR3 (IC50=69/37/108 nM), PDGFRα, and PDGFRβ (IC50=59/65 nM). Nintedanib has antitumor activity and inhibits tumor growth by inhibiting angiogenesis. |
| 細胞實驗 | HUVEC, HUASMC, and BRP were cultured as described above. Two hours before the addition of ligands, BIBF 1120 was added to the cultures. Cell lysates were generated according to standard protocols. Western blotting was done using standard SDS-PAGE methods, loading 50 to 75 μg of protein per lane, with detection by enhanced chemiluminescence. Total and phosphorylated mitogen-activated protein kinase (MAPK) was analyzed using monoclonal antibodies M3807 and M8159. Total Akt was detected using the polyclonal antibody and phosphorylated Akt (Ser473) was analyzed with the monoclonal antibody. Cleaved caspase-3 was detected with the monoclonal antibody [1]. |
| 激酶實驗 | The cytoplasmic tyrosine kinase domain of VEGFR-2 (residues 797–1355 according to sequence deposited in databank SWISS-PROT P35968) was cloned into pFastBac fused to GST and extracted as described in supplementary methods. Enzyme activity was assayed using standard conditions using a random polymer (Glu/Tyr 4:1) and in the presence of 100 μmol/L ATP (for details, see supplementary methods). For all other kinase assays, the entire cytoplasmic domains of the receptors (from the end of the transmembrane to the COOH terminus) were cloned into pFastBac vector containing GST and assayed under standard conditions [1]. |
| 動物實驗 | Five-week-old to 6-wk-old athymic NMRI-nu/nu female mice (21–31 g) were purchased from Harlan. After acclimatization, mice were inoculated with 1 to 5 × 10^6 (in 100 μL) FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 cells s.c. into the right flank of the animal. F344 Fischer rats after acclimatization were injected with 5 × 10^6 (in 100 μL) GS-9L cells s.c. into the right flank of the animal. For pharmacokinetic analysis, blood was isolated at indicated time points from the retroorbital plexus of mice and plasma was analyzed using high-performance liquid chromatography-mass spectrometry methodology [1]. |
| 體外活性 | 方法：人鼻咽癌細胞 CNE-2、HNE-1 和 HONE-1 用 Nintedanib (0.078-10 μM) 處理 72 h，使用 CCK8 assay 檢測細胞活力。
結(jié)果：Nintedanib 以劑量依賴的方式顯著抑制 CNE-2、HNE-1 和 HONE-1 細胞系的生長，IC50 值分別為 4.16 μM、5.62 μM 和 6.32 μM。[1]
方法：人內(nèi)皮細胞 HUVEC、平滑肌細胞 HUASMC 和牛視網(wǎng)膜周細胞用 Nintedanib (0.03-1 μM) 處理 2 h，使用 Western Blot 檢測靶點蛋白表達水平。
結(jié)果：Nintedanib 抑制 HUVEC、HUASMC 和牛視網(wǎng)膜周細胞中 MAPK 和 Akt 的配體依賴性磷酸化。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Nintedanib (10-100 mg/kg) 灌胃給藥給攜帶人頭頸部小細胞癌腫瘤 FaDu 或人腎癌腫瘤 Caki-1 的 athymic NMRI-nu/nu 小鼠，每天一次，持續(xù) 23-35 天。
結(jié)果：Nintedanib 抑制 FaDu 和 Caki-1 的腫瘤生長。[2]
方法：為檢測體內(nèi)抗腫瘤活性，將 Nintedanib (40 mg/kg) 和 TFTD (150 mg/kg) 腹腔注射給攜帶腫瘤 DLD-1、DLD-1/5-FU、HT-29 或 HCT116 的 BALB/c nu/nu 小鼠，每天兩次,持續(xù)兩周。
結(jié)果：在第 15 天，Nintedanib 和 TFTD 單藥治療療導致體內(nèi)腫瘤生長顯著減少。聯(lián)合療法表現(xiàn)出比兩種單一療法更大的抗腫瘤活性。[3] |
| 存儲條件 | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 0.6 mg/mL (1.11 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
Ethanol : 3 mg/mL (5.55 mM)
DMSO : 10 mg/mL (18.53 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
|
| 關(guān)鍵字 | FGFR | PDGFR | Inhibitor | Platelet-derived growth factor receptor | Fibroblast growth factor receptor | Vascular endothelial growth factor receptor | VEGFR | Nintedanib | BIBF1120 | inhibit | BIBF-1120 |
| 相關(guān)產(chǎn)品 | Imatinib | Amlexanox | Gilteritinib | Ribociclib | Formononetin | Axitinib | Lenvatinib mesylate | Ferulic Acid | Regorafenib | Pazopanib | Sorafenib | Regorafenib monohydrate |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 抗癌上市藥物庫 | 已知活性化合物庫 | EMA 上市藥物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | FDA 上市激酶抑制劑庫 |