Histone acetyltransferase GCN5 is a validated drug target for human diseases. Through structure-based virtual screening and similarity search of active hits, we discovered a potent GCN5 inhibitor DC_G16 with broad selectivity over a panel of other epigenetic targets. In vitro characterization of DC_G16 by fluorescence polarization (FP), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) demonstrated its high affinity binding to GCN5. Collectively, our data highlights DC_G16 as a promising lead compound and chemical probe targeting GCN5.
