Fragments in Drug Discovery

Thirty years ago, the study began into how very small molecules could have the ability to harness potential power as drug leads. These molecules have the benefit of being able to sample a large chemical space thanks to their small size which ranges from 150 to 300 Da. They were given the name fragments and, since then, seven of these fragments have been developed into FDA-approved clinical compounds.

From Vemurafenib for treatment of late-stage melanoma approved back in 2011, to Capivasertib for treatment of breast cancer that was just approved November 2023, fragment-based drug discovery has grown at an impressive rate and continues to do so. In addition to these seven FDA-approved compounds, fifty are in clinical trials including four in Phase 3.

Fragment-based drug discovery is a multidisciplinary approach that starts with the design of a fragment library all the way to growth of a promising fragment hit. This involves various screening and characterization methods, including a growing contribution by machine learning. But what goes into finding that potential hit compound that can make it all the way to the patients who need it?

In this collection, we want to highlight research that focuses on fragments in drug discovery. Have you found validated fragment hits for a new disease target? Maybe they unlocked an unreported enzyme mechanism? Were you able to develop a method that is useful for fragment-based drug discovery? Perhaps you found a hit that made it to clinical trials? We invite all scientists who work with fragments in the context of drug discovery to submit their interesting fragment stories. We look forward to hearing all about them.

Here we have also highlighted the most recent work on fragments that has been published with us. These include stories of fragment library design and updated screening methods, as well as recently developed approaches for validating, growing, merging, linking and optimizing fragment hits.