By analysing the physicochemical properties of a database of hits and leads, Keserü and Makara conclude that high-throughput screening, as well as hit-to-lead optimization practices in general, are responsible for the unfavourable physicochemical profile of recent leads and clinical candidates. Major adjustments may be needed to enable a balanced lead-evolution process and reduce the likelihood of high compound-related attrition in clinical trials.
- György M. Keserü
- Gergely M. Makara
