AZD4547
作者：齐岳
发布时间：2023-08-25
08:58:39
点击数：
产品名称：AZD4547
产品描述：
| 产品描述 | AZD4547, a new-type specific FGFR inhibitor, targets for FGFR1/2/3 (IC50: 0.2/2.5/1.8 nM in cell-free assays). |
| 靶点活性 | FGFR3:1.8 nM (cell free), FGFR1:0.9 nM (cell free), KDR:24 nM (cell free), FGFR2:2.5 nM (cell free) |
| 体外活性 | AZD4547 potently inhibits the tyrosine kinase activities of recombinant FGFR1/2/3 in vitro (IC50s: 0.2/2.5/1.8 nmol/L) and displays weaker activity against FGFR4 (IC50: 165 nmol/L). AZD4547 shown to inhibit recombinant VEGFR2 (KDR) kinase activity (IC50: 24 nmol/L). AZD4547 inhibited the proliferation of KG1a cells and KMS11 cells (IC50s: 18 and 281 nmol/L). Notably, MCF7 cell proliferation was unaffected by incubation with AZD4547 up to a concentration of 30 μmol/L [1]. Of 78 cell lines, only 2 (DMS114 and NCI-H1581) displayed a profound sensitivity to AZD4547, with GI50 values of 0.111 and 0.003 μmol/L, respectively [2]. |
| 体内活性 | Twice daily administration of AZD4547 at 3 mg/kg gave statistically significant tumor growth inhibition of 53% when compared with vehicle-treated controls, whereas doses of 12.5 mg/kg once daily and 6.25 mg/kg twice daily resulted in complete tumor stasis. A further efficacy study in the KG1a model with 12.5 mg/kg once daily AZD4547 resulted in 65% tumor growth inhibition [1]. Tumor-bearing mice were randomly grouped and dosed orally, once daily with vehicle, 3.125, 6.25, or 12.5 mg/kg AZD4547 for a period of 15 days. Potent tumor regressions were observed in the 6.25 and 12.5 mg/kg treatment groups, whereas tumor stasis followed by slow regrowth was observed in the 3.125 mg/kg treatment group [2]. |
| 激酶实验 | Cells were treated with AZD4547 or control for 3 hours at 37°C and then stimulated with 10 ng/mL aFGF/bFGF and 10 μg/mL heparin for 20 minutes. Western blotting was conducted with standard SDS-PAGE procedures and antibody incubation carried out overnight at 4°C. Secondary antibodies were applied and immunoreactive proteins visualized with Chemiluminescence substrate according to the manufacturer's instructions [1]. |
| 细胞实验 | Cell lines were incubated with fixed concentrations of AZD4547 for 72 hours. For fluorescence-activated cell sorting (FACS), cells were fixed with 70% ethanol and then incubated with propidium iodide/RNase A labeling solution. Cell-cycle profiles were assessed with a FACSCalibur instrument and CellQuest analysis software. For apoptotic analysis, cells and media were gently harvested and centrifuged, followed by washing of cell pellets. Cells were then processed for Annexin V-fluorescein isothiocyanate (FITC) staining and propidium iodide uptake according to the manufacturer's instructions. The proportion of cells staining positive for Annexin V were then assessed with a FACSCalibur instrument and quadrant sorting was done by CellQuest analysis software [1]. |
| 动物实验 | Tumor xenografts were established by s.c. injection into the left flank with 0.1 mL tumor cells (1 × 10^6 for LoVo, 1 × 10^7 for HCT-15, and 1 × 10^7 for Calu-6) or 0.2 mL (2 × 10^7 for KMS11 and KG1a) mixed 1:1 with Matrigel, with the exception of LoVo and HCT-15, which did not include Matrigel. Mice were randomized into control and treatment groups when tumors reached the determined size of more than 0.2 cm3. Tumor volume (measured by caliper), animal body weight, and tumor condition were recorded twice weekly for the duration of the study. Tumor volume was calculated as described previously [1]. |
| 分子量 | 463.582 |
| 分子式 | C26H33N5O3 |
| CAS No. | 1035270-39-3 |
存储
| Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
DMSO: 85 mg/mL (183.4 mM)
Ethanol: <1 mg/mL
H2O: <1 mg/mL
( < 1 mg/mL refers to the product slightly soluble or insoluble )
联系我们：
邮箱：2519696869@qq.com
QQ: 2519696869
电话：18066853083
微信：18066853083
公司介绍：
西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
主营产品：COF、MOF单体系列：三蝶烯衍生物、金刚烷衍生物、四苯甲烷衍生物、peg、上转换、石墨烯、光电材料、点击化学、凝集素、载玻片、蛋白质交联剂、脂质体、蛋白、多肽、氨基酸、糖化学等。
