qHTS to Identify Small Molecule GUS Inhibitors

National Center For Advancing Translational Sciences

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Linked publications & trials

Abstract

As such, this project aims to screen the chemical libraries at NCATS against a novel, disease relevant microbiome target to identify promising hits that can be further developed and optimized into tomorrows symbiotic drugs. After establishing the collaborative framework for this project, a high-throughput assay against a key ortholog from the GUSsome was optimized, miniaturized, and implemented to identify at least several different chemical series as hits. Purified resynthesized and procured powders have been used for hit validation and followed by detailed characterization of hit activity against a diverse panel of bacterial GUS enzymes. Four different chemical series are now poised for medicinal chemistry SAR-driven optimization to further improve their activity and selectivity.