神经药理学报2024，Vol.14Issue(5)：10-18,9.DOI:10.3969/j.issn.2095-1396.2024.05.002
喹唑啉类FGFR4抑制剂的三维定量构效关系研究
Three-Dimensional Quantitative Structure-Activity Relationship Study of Quinazoline-Based FGFR4 Inhibitors
摘要
Abstract
Objective:The abnormal activation of the Fibroblast Growth Factor 19(FGF19)and Fibroblast Growth Factor Receptor 4(FGFR4)signaling pathway promotes the proliferation of hepatocellular carcinoma cells,making FGFR4 one of the key targets for treating hepatocellular carcinoma.This study aims to elucidate the relationship between the structure and activity of quinazoline-based FGFR4 inhibitors using a three-dimensional quantitative structure-activity relationship(3D-QSAR)approach.Methods:36 compounds were randomly divided into a training set and a test set.3D-QSAR models were constructed using Comparative Molecular Field Analysis(CoMFA)and Comparative Molecular Similarity Indices Analysis(CoMSIA).Results:The cross-validation coefficients(q2)of the CoMFA and CoMSIA models were 0.735 and 0.680,respectively,and the fitting validation coefficients(r2)were 0.974 and 0.981,respectively.The predicted values of the two models were generally consistent with the experimental values,indicating that the models have predictive ability and good robustness.Conclusion:The contour maps illustrate the effects of different field effects on compound activity,providing insights for the design of novel quinazoline-based FGFR4 inhibitors.关键词
FGFR4抑制剂/三维定量构效关系/CoMFA/CoMSIAKey words
FGFR4 inhibitor/3D-QSAR/CoMFA/CoMSIA分类
医药卫生引用本文复制引用
路晨轩,陈茁茁,李国峰,刘星媛,孟宏,覃语涵,李亚鑫..喹唑啉类FGFR4抑制剂的三维定量构效关系研究[J].神经药理学报,2024,14(5):10-18,9.基金项目
国家级大学生创新训练计划项目(No.202410092003) （No.202410092003）
河北省省级大学生创新训练计划项目(No.S202410092021) （No.S202410092021）
