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Updated: Jun 12, 2025

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
Published on: August 17, 2019
Human F-ATP synthase as a drug target
Christoph Gerle1, Chimari Jiko2, Atsuki Nakano3
1Life Science Research Infrastructure Group, RIKEN SPring-8 Center, Kouto, 1-1-1, Sayo, Hyogo, Japan.
Abstract:
Practical and conceptual barriers have kept human F-ATP synthase out of reach as a target for the treatment of human diseases. Although this situation has persisted for decades, it may change in the near future. In this review the principal functionalities of human F-ATP synthase--proton motive force / ATP interconversion, membrane bending and mitochondrial permeability transition--are surveyed in the context of their respective potential for pharmaceutical intervention. Further, the technical requirements necessary to allow drug designs that are effective at the multiple levels of functionality and modality of human F-ATP synthase are discussed. The structure-based development of gastric proton pump inhibitors is used to exemplify what might be feasible for human F-ATP synthase. And finally, four structural regions of the human F-ATP synthase are examined as potential sites for the development of structure based drug development.
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