MAX4Life Talk Series: Accelerating Drug Discovery

Welcome Dr. Daren Fearon from Diamond Light Source as the first speaker in the MAX4Life Talk Series for autumn 2025!

The MAX4Life series highlights innovative and impactful Life Science research through one-hour talks, followed by Q&A and informal mingling with the MAX IV community.

Talk Title: “Accelerating Drug Discovery with High-Throughput Crystallographic Fragment Screening and Structural Enablement”

Dr. Fearon will present how the XChem platform has transformed fragment-based lead discovery (FBLD) by integrating sample prep, automated data collection, and structure-based progression into a high-throughput workflow.

Time & Date: 13:00 on Tuesday, 18th November

Location: meeting room MAX III, MAX IV Laboratory

Please use the Zoom link if attending remotely.

Dr. Fearon will be at MAX IV for the full day on the 18th of November, we encourage interested researchers to engage with him during his visit.

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Abstract:

Accelerating drug discovery with high-throughput crystallographic fragment screening and structural enablement

Daren Fearon – Diamond Light Source, Research Complex at Harwell

Fragment-based lead discovery (FBLD) has developed into a widely used strategy for identifying chemical matter with high ligand efficiency and tractable optimization pathways. Among available screening modalities, X-ray crystallography provides unparalleled structural insight and sensitivity, but has historically been constrained by limited throughput and operational complexity.

Over the last decade, the XChem platform at Diamond Light Source has been developed as a pioneering facility for high-throughput crystallographic fragment screening (CFS). The platform integrates sample preparation, automated data collection, hit identification, and structure-based fragment progression into a seamless workflow.

This presentation outlines our operational approach and lessons from running XChem as both a user-accessible resource and a central component of the antiviral drug discovery (AViDD) pipeline. Case studies illustrate how early structural data enabled the progression of fragment hits to lead molecules, including an example where iterative structure-guided development resulted in orally bioavailable dual inhibitors of SARS-CoV-2 and MERS main proteases, achieving clinical potential in under five years.

We further highlight enhancements to the pipeline that broaden opportunities for fragment progression and reduce the time from initial screening to lead identification. Together, these advances position CFS as an efficient, scalable and versatile approach for both academic and industrial drug discovery projects.

References

• Fearon, D., et al. (2024). Accelerating drug discovery with high-throughput crystallographic fragment screening and structural enablement. Applied Research, 4.
• Douangamath, A., Powell, A., Fearon, D., et al. (2021). Achieving efficient fragment screening at XChem facility at Diamond Light Source. Journal of Video Evidence, 271.
• Erlanson, D., et al. (2025). Where and how to house big data on small fragments. Nature Communications, 16, 4179.
• Boby, M. L., Fearon, D., Ferla, M., Filep, M., Koekemoer, L., Robinson, M. C., et al. (2023). Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors. Science, 382, 6671.