Early Drug Discovery

Small molecule drug discovery is a major focus of research of the Astbury Centre. We have significant capability in the identification and optimisation of small molecule modulators of proteins for a wide-range of target classes (from enzymes to protein-protein interactions) to support both the understanding of biological mechanism and structure (pharmacological tool compounds) and as potential starting points for future drug discovery (hits and leads). We are highly multidisciplinary, with researchers working on chemical synthesis, medicinal chemistry, computer-aided drug design, biomolecular structure determination, assay design and screening, and involving both in vitro and in vivosystems. This often involves undertaking work in collaboration with Industry and groups at Universities across the UK and beyond.

Once molecules of interest have been created researchers in the Centre make use of the wide number of tools and technologies available to determine their ability to bind to their target and have the desired outcome in vitro and in vivo, including X-ray crystallography, NMR and EM for structure determination, SPR/ITC/MST for binding, confocal miscopy high-throughput screening, diversity-orientated synthesis, fragment-based design, as well as chemical proteomic approaches to manipulate and label proteins.

Current major directions include:

• A pipeline of hit-to-lead and lead optimization small molecule drug discovery programmes targeting areas of major unmet medical need
• The design and synthesis of diverse, novel and lead-like chemical scaffolds through diversity orientated synthesis
• The development of novel chemical approaches to target protein-protein interactions.

Outputs of our research offer new strategies to more effectively modulate targets or target classes as well as to provide opportunities to intervene in many pathological processes