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PIM-1 kinase has been widely considered as attractive target for the development of anticancer drugs.1,2,3-triazolo[4,5-b]pyridines (TPs) have been recently identified as a new class of PIM-1 kinase inhibitors.A computational strategy based on molecular docking studies, followed by docking-based comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), has been used to elucidate the atomic details of the PIM-1/TPs interactions and to identify the most important features impacting the TPs inhibitory activity.While the 3D-QSAR models were created based on a training set of 32 compounds, their external predictivity was validated using a test set of 11 compounds.The best CoMFA model yielded the non-cross validation rncv2 =0.916, cross validation rcv2 =0.490 and predictive rpred2=0.753.The best CoMSIA model yielded a non-cross validation rncv2 =0.924, cross validation rcv2 =0.524 and predictive rpred2=0.766.Both the two 3D QSAR models can successfully predict the compound activity.