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Cambridge MedChem Consulting

Learning from our mistakes: The ‘unknown knowns’ in fragment screening

Whilst fragment-based screening has been around for a while there are still groups that are new to the area. This invaluable paper provides an insight into the pit-falls that await the unwary scientist. Absolutely essential reading

In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection methods are pushed to their limits, leading to a variety of artifacts, false positives, and false negatives that too often go unrecognized. This Digest discusses some of these problems and offers suggestions to avoid them. Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening.

Learning from our mistakes: The ‘unknown knowns’ in fragment screening DOI