store at low temperture,keep away from moisture,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Axitinib 是一种多靶点酪氨酸激酶抑制剂,能够抑制 VEGFR1 (IC50:4 nM),VEGFR2 (IC50:20 nM),VEGFR3 (IC50:0.4 nM),PDGFRβ (IC50:2 nM)。
产品描述 | Axitinib is an orally bioavailable tyrosine kinase inhibitor with IC50s of 0.1, 0.2, 0.1-0.3, 1.7, 1.6 nM for VEGFR1, VEGFR2, VEGFR3, c-kit, and PDGFRβ, respectively. |
靶点活性 | PDGFRβ:1.6 nM, Kit:1.7 nM, VEGFR1/FLT1:0.1 nM, VEGFR2/KDR: 0.2 nM, VEGFR2/Flk1:0.18 nM, VEGFR3: 0.1-0.3 nM |
体外活性 | In transfected or endogenous RTK-expressing cells, axitinib potently blocked growth factor-stimulated phosphorylation of VEGFR-2 and VEGFR-3 (IC50s: 0.2 and 0.1 to 0.3 nmol/L, respectively). Cellular activity against VEGFR-1 was 1.2 nmol/L. Axitinib rapidly and dose-dependently reduced the phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinase 1/2 (ERK1/2), key downstream signaling molecules of VEGF [1]. Axitinib reduced cell viability in a dose-dependent manner with IC50 doses of >10,000, 849 and 274 nmol/l for IGR-N91, IGR-NB8, and SH-SY5Y, respectively. the sensitivity to axitinib of neuroblastoma cell lines appeared to be in a similar range as non-VEGF stimulated HUVEC (IC50: 573 nmol/l) [2]. |
体内活性 | Acute axitinib treatment rapidly and significantly reduced retinal vascular VEGFR-2 phosphorylation. One hour after the second dose, retinal VEGFR-2 phosphorylation was reduced by 80% to 90% compared with that of the control tissues. Six and 24 to 32 h post-dose, the phospho-VEGFR-2 levels returned to ~50% and 100% of the control, respectively. The EC50 value for the inhibition of VEGFR-2 phosphorylation was 0.49 nmol/L [1]. Mice were next treated for a period of 2 weeks with either fractionated radiation (5 × 2 Gy/wk) or AG-013736 (25 mg/kg/d) and 1 to 3 weeks for the combination. Tumor volume at the end of 2 weeks was significantly reduced for either single or combination treatments. Percentage increases in tumor volume were similar between radiotherapy (40 ± 9.8%) and AG-013736 (48 ± 9.2%), and the combination was markedly reduced versus controls (12 ± 5.7% versus 77 ± 11%) [3]. |
激酶实验 | 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]. |
细胞实验 | 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]. |
动物实验 | 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]. |
别名 | AG-013736, 阿昔替尼, 阿西替尼 |
分子量 | 386.47 |
分子式 | C22H18N4OS |
CAS No. | 319460-85-0 |
store at low temperture,keep away from moisture,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 2 years
DMSO: 9.7 mg/mL (25 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
bottom
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Axitinib 319460-85-0 Angiogenesis Tyrosine Kinase/Adaptors c-Kit PDGFR VEGFR inhibit AG013736 Platelet-derived growth factor receptor Inhibitor Vascular endothelial growth factor receptor AG-013736 阿昔替尼 AG 013736 阿西替尼 inhibitor