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Updated: Feb 19, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Current perspectives in fragment-based lead discovery (FBLD)
Bas Lamoree1, Roderick E Hubbard2,3
1York Structural Biology Laboratory (YSBL), Department of Chemistry, University of York, Heslington, York YO10 5DD, U.K.
Abstract:
It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most 'conventional' targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein-protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery - generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology - providing chemical tools to investigate biological molecules, mechanisms and systems.
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