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Updated: Feb 9, 2026

Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors
Published on: June 27, 2025
A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinases
Lalit Kumar Sharma1, Roberta Leonardi, Wenwei Lin
1Department of Chemical Biology and Therapeutics, ‡Department of Infectious Diseases, St. Jude Children's Research Hospital , 262 Danny Thomas Place, Memphis, Tennessee 38105, United States.
Abstract:
Pantothenate kinase (PanK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. The association of PanK with neurodegeneration and diabetes suggests that chemical modifiers of PanK activity may be useful therapeutics. We performed a high throughput screen of >520000 compounds from the St. Jude compound library and identified new potent PanK inhibitors and activators with chemically tractable scaffolds. The HTS identified PanK inhibitors exemplified by the detailed characterization of a tricyclic compound (7) and a preliminary SAR. Biophysical studies reveal that the PanK inhibitor acts by binding to the ATP-enzyme complex.
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