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Updated: Aug 22, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Pharmacological targeting of GCN5/PCAF (KAT2A/B): current drug discovery strategies and translational potential
Priyanka Pandey1, Prajjval Mishra1, Pritam Biswas2
1Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, India.
Abstract:
The catalytic activity of general control non-derepressible 5 (GCN5) and p300/CBP-associated factor (PCAF) plays a pivotal role in numerous physiological and pathological conditions, underscoring its potential as a therapeutic target. However, developing clinically viable modulators remains challenging due to highly conserved catalytic domains within the GCN5-related N-acetyltransferases family. Recent advances have shifted the focus from classical catalytic-site inhibitors to noncatalytic-domain inhibitors, improving selectivity and specificity. Emerging approaches, including proteolysis-targeting chimeras, acetylation-targeting chimeras, high-throughput screening and rational drug design, are reshaping the landscape of inhibitor development. This review outlines the structural features, functions and diverse roles of GCN5/PCAF in disease pathology, with an emphasis on inhibitor design strategies. We also propose a framework for inhibitor development that integrates active-site engagement, pharmacophore modelling and function-driven targeting strategies to bridge the gap between early-stage discovery and translational potential.
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