Fig. 2

The current HAT inhibitors and activators. Bi-substrate inhibitors mimic the two HAT substrates: Ac-CoA, connected via a linker to a peptide resembling the lysine substrate. Garcinol, curcumin, and anacardic acid are natural product HAT inhibitors. Small molecule inhibitors C646 and thiazinesulfonamide were discovered from a virtual screening. A high throughput screening yielded isothiazolone derivatives. A pentamidine derivative, TH1834, and a benzylidene barbituric acid derivative were developed using a structure-based design. ICG-001 is a protein–protein interaction inhibitor and inhibits the interaction between KAT3A and β-catenin. HAT bromodomain inhibitors have been developed for KAT3A and KAT2B, including the natural product ischemin, a set of cyclic peptides and small molecule N1-aryl-propane-1,3-diamine derivatives. CTPB, TTK21, and SPV106 are salicylic acid-derived HAT activators. CTBP activates KAT3B, TTK21 activates both KAT3B and KAT3A, and SPV106 interestingly is a KAT2B activator and KAT3A/3B inhibitor