Crystallographic fragment screening has emerged relatively recently as the most efficient biophysical screening method. Screening a fragment library against a drug target in fragment-based drug discovery (FBDD) is widely used at the early stages of discovery projects to identify new hits that can be developed into lead molecules. An X-ray structure enables direct observation of fragment binding while allowing for the analysis of the details of its interactions with the protein. This provides a clear advantage for the subsequent steps of hit expansion and lead generation. The SARomics Biostructures CRO team has extensive experience in all forms of fragment screening services, including crystallographic fragment screening. At the recent (2025) Fragment-Based Lead Discovery Conference (FBLD Conference) in Cambridge, UK, SARomics Biostructures AB presented a new kinase-focused fragment library for crystallographic fragment screening. The library has been developed in collaboration with Jens Carlsson, Szymon Pach, and Philip Ullmann (Uppsala University), with the focus on generating a fragment library containing sociable and water-soluble fragments that can be rapidly expanded using analogues from the Enamine REAL library. The designed kinase-focused fragment library, comprising 300 compounds, was tested against two kinases (CDK2 and an internal target) using the FragMax fragment screening platform, yielding hit rates of 13% to 16%. The hits were subsequently ranked using a combination of differential scanning fluorimetry (DSF) and free-energy calculations based on molecular dynamics (MD) simulations, followed by the selection and ranking of follow-up analogues using docking for hit expansion. As a CRO, we operate within the framework of our agreement with MAX IV Laboratory, which means our clients do not need to apply for beamtime or for accessing crystallographic fragment screening facilities.
