The advancement of high-throughput chemistry and high-throughput screening has led to the rapid identification of workable hits for drug discovery. However, the hit-to-lead and lead-to-candidate processes are still relatively slow. As such, computational approaches to quickly identify bioisosteric replacements have been applied to improve the efficiency of the drug discovery processes.

In this talk we will discuss the application of a shape- and electrostatic-based bioisosteric replacement approach developed at GSK, using ROCS (OpenEye Scientific Software, Santa Fe, NM) for the shape matching and EON (also from OpenEye) to evaluate electrostatic similarity. This ROCS/EON workflow has been used to virtually screen fragment databases for bioisosteric replacements, and results for 7TM and ion channel projects will be presented.