| 名稱 | Axitinib |
| 描述 | Axitinib (AG-013736) is a multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1, VEGFR2, VEGFR3, and PDGFRβ (IC50=4/20/0.4/2 nM). Axitinib has antitumor activity and is used in the treatment of renal cell carcinoma. |
| 細(xì)胞實驗 | Endothelial or tumor cells were starved for 18 h in the presence of either 1% FBS (HUVEC) or 0.1% FBS (tumor cells). Axitinib was added and cells were incubated for 45 min at 37°C in the presence of 1 mmol/L Na3VO4. The appropriate growth factor was added to the cells, and after 5 min, cells were rinsed with cold PBS and lysed in the lysis buffer and a protease inhibitor cocktail. The lysates were incubated with immunoprecipitation antibodies for the intended proteins overnight at 4°C. Antibody complexes were conjugated to protein A beads and supernatants were separated by SDS-PAGE. The Super Signal West Dura kit was used to detect the chemiluminescent signal [1]. |
| 激酶實驗 | Porcine aorta endothelial (PAE) cells overexpressing full-length VEGFR-2, PDGFR-β, KIT, and NIH-3T3 overexpressing murine VEGFR-2 (Flk-1) or PDGFR-α were generated as described previously. The ELISA capture plates were prepared by coating 96-well ReactiBind plates with 100 μL/well of 2.5 μg/mL anti-VEGFR-2 antibody, 0.75 μg/mL anti-PDGFR-β antibody, 0.25 μg/mL anti-PDGFR-α antibody, 0.5 μg/mL anti-KIT antibody, or 1.20 μg/mL anti-Flk-1 antibody. Measurement of RTK phosphorylation by ELISA was done as described previously [1]. |
| 動物實驗 | AG-013736, a receptor kinase inhibitor of VEGFRs and, at higher doses, PDGFRs (IC50 = 0.1 nmol/L for VEGFR-1, 0.2 nmol/L for VEGFR-2, 0.1–0.3 nmol/L for VEGFR-3, and 1.6 nmol/L for PDGFRβ; ref. 18), was provided by Pfizer Global Research and given once daily by gavage in a volume of 0.13 mL. Control animals received 0.5% carboxymethylcellulose drug carrier. Irradiations were done on nonanesthetized mice using a 137Cs source operating at 2.4 Gy/min. Mice were confined to plastic jigs with tumor-bearing legs extended through an opening in the side, allowing local irradiations. Fractionated doses were given in five daily 2 Gy fractions per week (omitting weekends). For combination treatments, radiotherapy was delivered first, and AG-013736 was given within ～4 h. Mice were sacrificed, and tumors were excised and then quick frozen (using liquid nitrogen) following 1, 2, or 3 weeks of treatment [3]. |
| 體外活性 | 方法：膠質(zhì)瘤細(xì)胞 U87、T98 和 U251 用 Axitinib (0.1-100 μM) 處理 72 h，通過 MTT assay 測定細(xì)胞活力。
結(jié)果：治療 72 h 后，Axitinib 抑制 U87 和 T98 細(xì)胞的生長，IC50 值分別為 12.7 μM 和 8.5 μM。相反，U251 細(xì)胞對 Axitinib 介導(dǎo)的細(xì)胞毒性作用更具抵抗力。[1]
方法：人上皮卵巢癌細(xì)胞 A2780、RMG1、HeyA8 和 HeyA8-MDR 用 Axitinib (1-4 μM) 處理 4 h，通過 Western Blot 檢測靶點蛋白表達(dá)水平。
結(jié)果：不同劑量的 Axitinib 治療以劑量依賴的方式顯著降低了 A2780、RMG1 和 HeyA 8中磷酸化 EGFR2 的表達(dá)，但在 HeyA8 MDR 細(xì)胞中沒有。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Axitinib (30 mg/kg，0.5% methyl cellulose) 口服給藥給攜帶 A2780、RMG1 或 HeyA8 MDR 腫瘤的 BALB/c nude 小鼠，每天兩次，持續(xù) 35-40 天。
結(jié)果：在 A2780 和 RMG1 模型中，Axitinib 治療組的腫瘤重量與對照組相比顯著降低了 50%，但在 HeyA8 MDR 模型中差異不顯著。[2] |
| 存儲條件 | store at low temperature,keep away from moisture,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 | DMSO : 9.7 mg/mL (25 mM)
|
| 關(guān)鍵字 | inhibit | Platelet-derived growth factor receptor | Inhibitor | Axitinib | Vascular endothelial growth factor receptor | AG013736 | VEGFR | AG 013736 | PDGFR |
| 相關(guān)產(chǎn)品 | Imatinib | Gilteritinib | Ribociclib | Sorafenib tosylate | Lenvatinib mesylate | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Pexidartinib | Regorafenib monohydrate | Taxifolin |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | FDA 上市藥物庫 | 膜蛋白靶向化合物庫 | FDA 上市激酶抑制劑庫 | 酪氨酸激酶分子庫 | 抗癌藥物庫 |