| 名称 | Cabozantinib |
| 描述 | Cabozantinib (XL184) is a multi-targeted tyrosine kinase receptor inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt3 (IC50=0.035/1.3/4.6/7/11.3 nM). Cabozantinib exhibits both antitumor and antiangiogenic activity. |
| 细胞实验 | Receptor phosphorylation of MET, VEGFR2, AXL, FLT3, and KIT were, respectively, assessed in PC3, HUVEC, MDA-MB-231, FLT3-transfected BaF3, and KIT-transfected MDA-MB-231 cells. Cells were serum starved for 3 to 24 hours, then incubated for 1 to 3 hours in serum-free medium with serially diluted cabozantinib before 10-minute stimulation with ligand: HGF (100 ng/mL), VEGF (20 ng/mL), SCF (100 ng/mL), or ANG1 (300 ng/mL). Receptor phosphorylation was determined either by ELISA using specific capture antibodies and quantitation of total phosphotyrosine or immunoprecipitation and Western blotting with specific antibodies and quantitation of total phosphotyrosine. Total protein served as loading controls [1]. |
| 激酶实验 | The inhibition profile of cabozantinib against a broad panel of 270 human kinases was determined using luciferase-coupled chemiluminescence, 33P-phosphoryl transfer, or AlphaScreen technology. Recombinant human full-length, glutathione S-transferase tag or histidine tag fusion proteins were used, and half maximal inhibitory concentration (IC50) values were determined by measuring phosphorylation of peptide substrate poly(Glu, Tyr) at ATP concentrations at or below the Km for each respective kinase. The mechanism of kinase inhibition was evaluated using the AlphaScreen Assay by determining the IC50 values over a range of ATP concentrations [1]. |
| 动物实验 | Female nu/nu mice were housed according to the Exelixis Institutional Animal Care and Use Committee guidelines. H441 cells (3 × 10^6) were implanted intradermally into the hind flank and when tumors reached approximately 150 mg, tumor weight was calculated using the formula: (tumor volume = length (mm) × width^2 (mm^2)]/2, mice were randomized (n = 5 per group) and orally administered a single 100 mg/kg dose of cabozantinib or vehicle. Tumors were collected at the indicated time points. Pooled tumor lysates were subjected to immunoprecipitation with anti-MET and Western blotting with anti-phosphotyrosine MET. After blot stripping, total MET was quantitated as a loading control. In a separate experiment, naive mice (n = 5 per group) were administered a single 100 mg/kg dose of cabozantinib or vehicle, followed by intravenous administration of HGF (10 μg per mouse) 10 minutes before liver collection. Analysis of MET phosphorylation in liver lysates was as described above. In a separate experiment, naive mice (n = 5 per group) were administered a single 100 mg/kg dose of cabozantinib or vehicle, followed by intravenous administration of VEGF (10 μg per mouse) 30 minutes before lung collection. Pooled lung lysates were subjected to immunoprecipitation with FLK1 and Western blotting with anti-phosphotyrosine. After blot stripping, total FLK1 was quantitated as a loading control [1]. |
| 体外活性 | 方法：前列腺癌细胞 LNCaP、C4-2B 和 PC-3 用 Cabozantinib (0.01-5 µM) 处理 72 h，使用 WST-1 Assay 检测细胞活力。
结果：Cabozantinib 以剂量依赖的方式抑制 LNCaP、C4-2B 和 PC-3 细胞系的细胞活力。[1]
方法：人肾癌细胞 786-O 和 A498 用 Cabozantinib (10-100 nM) 处理 1 h，随后用 HGF (1 nM) 刺激 20 min，使用 Western Blot 检测靶点蛋白表达水平。
结果：10 nM Cabozantinib 处理抑制了 HGF 激活的 pMET、pAKT、pERK 和 p-mTOR。[2] |
| 体内活性 | 方法：为检测体内抗肿瘤活性，将 Cabozantinib (60 mg/kg) 口服给药给胫骨内注射前列腺癌细胞 Ace-1 的 SCID 小鼠，每天一次，持续五周。
结果：Cabozantinib 抑制 Ace-1 细胞在体内的进展。[1]
方法：为检测体内抗肿瘤活性，将 Cabozantinib (1-60 mg/kg) 口服给药给携带肿瘤 MDA-MB-231、H441 或 C6 的 nu/nu 小鼠，每天一次，持续 12-14 天。
结果：Cabozantinib 以剂量依赖的方式抑制肿瘤生长。[3] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (99.7 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 9.3 mg/mL (18.54 mM), Suspension. Working solution is recommended to be prepared and used immediately.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | CD135 | angiogenesis | c-Kit | TAM Receptor | CD117 | Tyro3 | HT1080 | Fms like tyrosine kinase 3 | Inhibitor | Axl | A431 | VEGFR | antiangiogenic | FLT3 | c-Met/HGFR | BMS 907351 | B16F10 cells | SCFR | Apoptosis | inhibit | BMS907351 | XL-184 | Cabozantinib | Vascular endothelial growth factor receptor | Cluster of differentiation antigen 135 | XL 184 | Mer |
| 相关产品 | Stavudine | L-Ascorbic acid | Sodium 4-phenylbutyrate |
| 相关库 | 经典已知活性库 | 抗癌活性化合物库 | 抗癌上市药物库 | 已知活性化合物库 | EMA 上市药物库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 抗癌临床化合物库 |