Three dimensional pharmacophore modelling for c-Kit receptor tyrosine kinase inhibitors

Three Dimensional Pharmacophore model was developed based on 24 currently available c-Kit inhibitors. The best pharmacophore model (Hypo1) consists of four features namely one hydrogen bond acceptor, one hydrophobic point and two ring aromatics. The correlation coefficient, root mean square deviation and cost difference were 0.973, 0.729 and 100.989 respectively, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of 40 known c-Kit inhibitors in our test set with a correlation coefficient of 0.709 with a cross validation of 95% confidence level. Accordingly, our model is reliable in identifying new compounds as c-Kit inhibitors.

Graphical abstractThree Dimensional Pharmacophore model was developed based on 24 currently available c-Kit inhibitors. The best pharmacophore model (Hypo1) consists of four features namely one hydrogen bond acceptor, one hydrophobic point and two ring aromatics. The correlation coefficient, root mean square deviation and cost difference were 0.973, 0.729 and 100.989 respectively, suggesting that a highly predictive pharmacophore model was successfully obtained. The pharmacophore model generated can be used as three dimensional query in database searches to design new molecules and predicting their activity.Figure optionsDownload full-size imageDownload as PowerPoint slide