General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors.

A general pharmachophore model for various types of Ser/ Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/ Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/ Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3-5 n m range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained. [ABSTRACT FROM AUTHOR]