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Identifying and Optimising New Chemotypes for BRPF1b Inhibition with Grating-Coupled Interferometry

The efficient sampling of the chemical universe is at the heart of the fragment screening hit identification paradigm. The smaller the fragments, the more effcient the sampling. How small we can go is determined by our abiloty to detect very weak binding events between small molecules and target proteins. At Concept Life Sciences, we develop a unique fragment screening platform combining a purpose-built collection efficiently sampling the biophysicsically accessible chemical universe with the cutting-edge Grating-Coupled Interferometry (GCI) technology. By operating in this biophysicsical " sweet spot", we believe we can identify the most efficient fragment hits in a matter of days; thus providing highly desirable start points for fragment hit optimisation campaigns, and a quicker path to candidate nomination. We report below the implementation of this novel platform to the BRPF1b bromodomain. Our study not only helped us identify 17 lean and diverse fragments binding BRPF1b, it also provided high quality binding kinetics information from the initial screening campaign; a valuable asset to accelerate all subsequent drug discovery phases.

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