Classification of kinase inhibitors using BCUT descriptors

BCUTs are an interesting class of molecular descriptor which have been prop osed for a number of design and QSAR type tasks. It is important to underst and what kind of information any particular descriptor encodes and to be ab le to relate this to the biological properties of the molecules. In this pa per we present studies with BCUTs for the classification of ATP site direct ed kinase inhibitors active against five different protein kinases: three f rom the serine/threonine family and two from the tyrosine kinase family.;In combination with a chemometric method, PLS discriminant analysis,the BCUTs are able to correctly classify the ligands according to their target. A no vel class of kinase inhibitors is correctly predicted as inhibitors of the EGFR tyrosine kinase. Comparison with other descriptor types such as two-di mensional fingerprints and three-dimensional pharmacophore-based descriptor s allows us to gain an insight into the level of information contained with in the BCUTs.