In 1999 researchers Tom Blundell and Chris Abell in the Departments of Biochemistry and Chemistry, in collaboration with Harren Jhoti, who had spent more than a decade in big pharma, pioneered the use of fragment-based drug discovery (FBDD) in the University, leading to the foundation of the company Astex and creating a shift in the way pharmaceutical companies discover new lead compounds for drug discovery. Over 40 compounds discovered using FBDD have reached clinical trials.
The idea behind the process is that a library of hundreds of small fragments can be used to identify hotspots on a protein target and then be elaborated to larger drug-like molecules. This allows exploration of chemical space more efficiently than using a million-compound library of larger drug-like molecules. The researchers tackled a series of fundamental scientific questions relating to applying X-ray crystallography to the screening of these small molecule fragments.
Astex Pharmaceuticals has used FBDD to discover two new highly successful anti-cancer drugs that appeared on the market in 2017 (Kisqali) and 2019 (Balversa). Kisqali has been approved for breast cancer by the US Food and Drug Administration and the European Medicines Agency, and Balversa has been used for urothelial cancer, with approval for marketing in the USA.
The FBDD approach led to the creation of jobs, including 140 at Astex alone, generated a large contribution to the economy, including $866 million for the sale of Astex and $480 million for Kisqali sales in 2019–2020, and the approval in 75 countries of three drugs that are creating a positive impact on the health and wellbeing of patients with breast and urothelial cancer and leukemia.