| 名称 | 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. |
| 细胞实验 | 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]. |
| 激酶实验 | 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]. |
| 动物实验 | 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]. |
| 体外活性 | 方法：人鼻咽癌细胞 CNE-2、HNE-1 和 HONE-1 用 Nintedanib (0.078-10 µM) 处理 72 h，使用 CCK8 assay 检测细胞活力。
结果：Nintedanib 以剂量依赖的方式显著抑制 CNE-2、HNE-1 和 HONE-1 细胞系的生长，IC50 值分别为 4.16 µM、5.62 µM 和 6.32 µM。[1]
方法：人内皮细胞 HUVEC、平滑肌细胞 HUASMC 和牛视网膜周细胞用 Nintedanib (0.03-1 µM) 处理 2 h，使用 Western Blot 检测靶点蛋白表达水平。
结果：Nintedanib 抑制 HUVEC、HUASMC 和牛视网膜周细胞中 MAPK 和 Akt 的配体依赖性磷酸化。[2] |
| 体内活性 | 方法：为检测体内抗肿瘤活性，将 Nintedanib (10-100 mg/kg) 灌胃给药给携带人头颈部小细胞癌肿瘤 FaDu 或人肾癌肿瘤 Caki-1 的 athymic NMRI-nu/nu 小鼠，每天一次，持续 23-35 天。
结果：Nintedanib 抑制 FaDu 和 Caki-1 的肿瘤生长。[2]
方法：为检测体内抗肿瘤活性，将 Nintedanib (40 mg/kg) 和 TFTD (150 mg/kg) 腹腔注射给携带肿瘤 DLD-1、DLD-1/5-FU、HT-29 或 HCT116 的 BALB/c nu/nu 小鼠，每天两次,持续两周。
结果：在第 15 天，Nintedanib 和 TFTD 单药治疗疗导致体内肿瘤生长显著减少。联合疗法表现出比两种单一疗法更大的抗肿瘤活性。[3] |
| 存储条件 | 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 | 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)
|
| 关键字 | FGFR | PDGFR | Inhibitor | Platelet-derived growth factor receptor | Fibroblast growth factor receptor | Vascular endothelial growth factor receptor | VEGFR | Nintedanib | BIBF1120 | inhibit | BIBF-1120 |
| 相关产品 | Amlexanox | Gilteritinib | Formononetin | Ferulic Acid | Pazopanib | Sorafenib |
| 相关库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | EMA 上市药物库 | 激酶抑制剂库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | FDA 上市激酶抑制剂库 | 抗癌临床化合物库 | 抗癌药物库 |