Session Chairs:
Michael Sofia, Pharmasett, Inc., USA
Raju Mohan, Exelixis, Inc., USA
Prior to committing significant lead optimization resources to a HTS, active extensive validation of the chemotype is required. Therefore, the "hit to lead" process has evolved as a distinct phase in medicinal chemistry, bridging the gap between lead generation and full medicinal chemistry lead optimization. This process typically entails assessment of the pool of screening actives, validation of progressible SAR within selected chemical series, an early understanding of potential toxicological or metabolic liabilities, a clear understanding of IP and freedom-to-operate scope, and demonstration of in vitro potency and early indications of in vivo efficacy where possible. New cheminformatics tools, high-throughput assays that support liability assessment and the application of rapid analoging to scope out SAR trends are only a few of the emerging technologies utilized in critical decision making in the hit-to-lead phase. This session will highlight real examples of hit to lead development and showcase the application of novel approaches and tools that help accelerate the process.