The SAR studies on FAP inhibitors as tumor-targeted agents

Structure activity relationship (SAR) of fibroblast activation protein alpha (FAP) inhibitors will be useful to evaluate bioactivities of candidates. To discuss SAR of FAP inhibitors, two alignment styles were carried out to build QSAR models of FAP inhibitors. HQSAR was used to construct 2D-QSAR after the selection of training set and test set by principal component analysis method. Meanwhile, 3D-QSAR models were constructed by comparative molecular field analysis and comparative molecular similarity indices analysis method and optimized by FOCUS method. All the QSAR models were validated by cross-validation and test set, and the targeted QSAR model was selected by comprehensive evaluation containing cross-validation coefficient, correlation coefficient and consistency with docking studies. The result suggests that 2D-QSAR model may be insufficient to evaluate SAR of FAP inhibitors, while 3D-QSAR model with S+H+D_F functional fields could be applied to characterize the SAR based on docking conformation alignment.