[摘要]：A high-throughput docking strategy for the filtering of in silico compds. and the generation of kinase-targeted libraries is described. Systematic docking and scoring in three kinase crystal 3D structures of 123 structurally diverse kinase ligands led to the detn. of six thresholds for each kinase. These thresholds were used as filters for the virtual screening of two collections of compds.: a collection of more than 2500 drugs and drug-like compds. (neg. control) and a kinase-targeted library of 1440 compds. This strategy was then exptl. validated by testing 60 compds. from the kinase-targeted library on 41 kinases from five different families. The 60 compds. were split into those passing all the thresholds and the others (30 compds. in each group). The overall hit enrichment was 6.70-fold higher in the first group, validating our approach for the generation of kinase-targeted libraries and the identification of scaffolds with high kinase inhibitory potential.
