机构：[1]College of Life Sciences, Sichuan Agricultural University, Ya’an, China[2]Chengdu Agricultural College, Chengdu, China[3]Sichuan Agricultural University Hospital, Ya’an, China[4]Sichuan Food Fermentation Industry Research and Design Institute, Chengdu, China
The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Forty eight known inhibitors were collected to establish 3 D-QSAR models and pharmacophore models, investigate the relationship between the activity and conformation of compounds, and verify the efficiency of pharmacophore. In Accelrys Discovery Studio 2016, the ZINC database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 μM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects.Communicated by Ramaswamy H. Sarma.
基金：
This work was supported by Applied Basic Research Program of Sichuan
Province Sichuan (No. 2019YJ0549), Sichuan Science and Technology
Department Seedling engineering program (No. 201958), Sichuan
Science and Technology program (No. 2019YFG0154).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
无
最新[2023]版：
大类|3 区生物学
小类|3 区生物物理4 区生化与分子生物学
第一作者：
第一作者机构：[1]College of Life Sciences, Sichuan Agricultural University, Ya’an, China
共同第一作者：
通讯作者：
通讯机构：[1]College of Life Sciences, Sichuan Agricultural University, Ya’an, China[*1]College of Life Sciences, Sichuan Agricultural University, Ya’an, 625014, China
推荐引用方式(GB/T 7714)：
Huang Lu,Wu Xulong,Fu Xiaoli,et al.Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors.[J].Journal of biomolecular structure & dynamics.2021,1-14.doi:10.1080/07391102.2021.1899049.
APA：
Huang Lu,Wu Xulong,Fu Xiaoli,Wang Haoxiang,Tang Biao...&Bu Tongliang.(2021).Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors..Journal of biomolecular structure & dynamics,,
MLA：
Huang Lu,et al."Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors.".Journal of biomolecular structure & dynamics .(2021):1-14
