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Updated: Feb 16, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Fragment-based discovery of a potent NAMPT inhibitor
Alla Korepanova1, Kenton L Longenecker1, Steve D Pratt1
1Research & Development, AbbVie, 1 North Waukegan Road, North Chicago, IL 60064, United States.
Abstract:
NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor.
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