Crystal-based fragment screening of novel protein targets linked to disease has truly come of age: Diamond's XChem facility has been operating a regular user program since 2015, with other synchrotrons soon to follow suit. A progression of user projects have confirmed the power of this approach to discover both diverse chemotypes and unexpected mechanisms of action, especially allosteric binders.
At the same time, the continued success in unearthing a rich array of fragment hits has now decisively shifted the bottleneck onto the question of how to translate hits into high potency leads. This challenge has highlighted the need for efficient and scalable methodologies in the areas of library design, label-free assays, computational compound design and the synthesis of complex lead molecules.
This symposium aims to highlight the opportunities that must be explored if routine fragment screening is to turn into routine lead discovery. The event will bring together speakers from diverse disciplines to help define the methodology, focus and goals for fragment screening in the coming years.