Discussion

Current drug discovery relies on a process being in place since the mid 1990s and uses mostly high-throughput-screening (HTS) of chemical compound libraries of a million or more distinct chemical entities, in part fragment-based screening (FBS) of several thousand entities and in part structure-based drug discovery (SBDD) for finding active compounds. This approach is partially successful, but does not fulfill all the requirements of modern drug discovery, in particular the needs of difficult & unprecedented targets and pathways.
Future lead discovery on molecular targets will be based on the seamless integration of all lead discovery disciplines, such as HTS, FBS, SBDD, virtual screening, focused and iterative screening processes. These processes will use integrative methods from biochemical, biophysical and cell-based assay technologies on defined molecular targets (‘target-based drug discovery’). That approach will be complemented by screening methods on physiological effects in disease-relevant assay systems (‘phenotypic drug discovery’) followed by target deconvolution strategies.

Lorenz Mayr will discuss current and future lead discovery strategies on molecular targets and pathways at AstraZeneca with examples for the newly established integrated approach in lead discovery:
• Overview of currently available lead discovery technologies
• Limitations of existing lead discovery technologies
• Case studies from target-based lead discovery
• Case studies from phenotypic lead discovery
• Integration of lead discovery strategies
• Summary and outlook