AZD4547 - FGFR 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAZD4547Cat. No.: HY-13330CAS No.: 1035270-39-3分式: CHNO分量: 463.57作靶点: FGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 300 mg/mL (647.15 mM)* means soluble

2、, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1572 mL 10.7859 mL 21.5717 mL5 mM 0.4314 mL 2.1572 mL 4.3143 mL10 mM 0.2157 mL 1.0786 mL 2.1572 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；

3、澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.39 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.39 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small

4、 Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.39 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AZD4547种有效的 FGFR 家族抑制剂，作于 FGFR1，FGFR2，FGFR3 和 FGFR4，IC50 分别为 0.2nM，2.5 nM，1.8 nM 和 165 nM。IC50 & Target FGFR1 FGFR2 FGFR3 FGFR40.2 nM (IC50) 2.5 nM (IC50) 1.8 nM (IC50) 165 nM (IC50)体外研究 AZD4547 also

5、inhibits recombinant VEGFR2 (KDR) kinase activity with an IC50 of 24 nM. In KG1a, Sum52-PE, MCF7, and KMS11 cell lines, AZD4547 potently inhibits autophosphorylation of FGFR1, 2, and 3tyrosine kinases (IC50 values of 12, 2, and 40 nM, respectively) and displays weaker inhibition of FGFR4cellular kin

6、ase activity (IC50=142 nM). Significantly weaker inhibitory activity is observed versus cellular KDRand IGFR ligand-induced phosphorylation (IC50 values of 258 and 828 nM, respectively), representingapproximately 20- and 70-fold selectivity over cellular FGFR1. Besides, AZD4547 potently inhibits FGF

7、Rphosphorylation and downstream signaling affected through FRS2, PLC, and MAPK at the cellular level 1.体内研究 Female SCID mice bearing KMS11 tumors are randomized and treated chronically with AZD4547 at a rangeof well-tolerated doses. Oral AZD4547 treatment results in dose-dependent tumor growth inhib

8、ition. Twicedaily administration of AZD4547 at 3 mg/kg gives statistically significant tumor growth inhibition of 53% (P 1.PROTOCOLCell Assay 1 Cell lines are incubated with fixed concentrations of AZD4547 for 72 hours. For fluorescence-activated cellsorting (FACS), cells are fixed with 70% ethanol

9、and then incubated with propidium iodide/RNase A labelingsolution. Cell-cycle profiles are assessed with a FACSCalibur instrument and CellQuest analysis software.For apoptotic analysis, cells and media are gently harvested and centrifuged, followed by washing of cellpellets. Cells are then processed

10、 for FITC staining and propidium iodide uptake. The proportion of cellsstaining positive for Annexin V are then assessed with a FACSCalibur instrument and quadrant sorting isdone by CellQuest analysis software 1.MCE has not independently confirmed the accuracy of these methods. They are for referenc

11、e only.Animal Mice 1Administration 1 Swiss derived nude (nu/nu) and severe combined immunodeficient mice (SCID) are used. Tumor xenograftsare established by s.c. injection into the left flank with 0.1 mL tumor cells (1106 for LoVo, 1107 for HCT-15,and 1107 for Calu-6) or 0.2 mL (2107 for KMS11 and K

12、G1a) mixed 1:1 with Matrigel, with the exception ofLoVo and HCT-15, which do not include Matrigel. Mice are randomized into control and treatment groups(AZD4547, 1.5-50 mg/kg, once daily or twice daily by oral gavage) when tumors reach the determined size ofmore than 0.2 cm3. Tumor volume (measured

13、by caliper), animal body weight, and tumor condition arerecorded twice weekly for the duration of the study. Tumor volume is calculated.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Sci Tran

14、sl Med. 2018 Jul 18;10(450). pii: eaaq1093. Sci Signal. 2019 May 28;12(583). pii: eaaw9450.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Gavine PR, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinasefamily. Cancer Res, 2012, 72(8),