AbstractA three-dimensional pharmacophore model was developed based on 25 currently available inhibitors, which were carefully
selected with great diversity in both molecular structure and bioactivity as required by HypoGen program in the Catalyst software,
for discovering new farnesyltransferase (FTase) inhibitors. The best hypothesis (Hypo1), consisting of four features, namely,
two hydrogen-bond acceptors, one hydrophobic point, and one ring aromatic feature, has a correlation coefficient of 0.949, a rootmean-
square deviation of 1.321, and a cost difference of 163.15, suggesting that a highly predictive pharmacophore model was successfully
obtained. The application of the model shows great success in predicting the activities of 227 known FTase inhibitors in our
test set with a correlation coefficient of 0.776 with a cross-validation of 98% confidence level. Accordingly, our model should be
reliable in identifying structurally diverse compounds with desired biological activity.