HAT1 Inhibitors

Histone Acetyltransferase 1 (HAT1) is a key enzyme in the epigenetic regulation of gene expression, primarily acetylating lysine residues on histone H4. This modification of histones plays a crucial role in the structure and function of chromatin, influencing gene expression, DNA repair, replication, and other nuclear processes. HAT1 inhibitors, therefore, provide a means to study and manipulate these fundamental cellular processes. Direct inhibitors of HAT1, such as Anacardic Acid, Garcinol, Curcumin, C646, and MB-3, function by binding to the active site of HAT1 or its acetyl-CoA binding site, impeding its ability to transfer acetyl groups to histones. These inhibitors are invaluable in studying the specific role of HAT1-mediated acetylation in various cellular contexts, including development, differentiation, and response to DNA damage.

Indirect inhibitors of HAT1 primarily include histone deacetylase (HDAC) inhibitors like Scriptaid, SAHA, Panobinostat, Chidamide, Entinostat, and Romidepsin. These compounds do not target HAT1 directly but influence the acetylation status of histones by inhibiting HDACs. This indirect approach can alter the dynamic balance between acetylation and deacetylation, affecting HAT1's functional landscape. Additionally, compounds like BIX01294, though primarily targeting other epigenetic modifiers, can indirectly modulate HAT1 activity by influencing the overall chromatin structure and histone modification landscape.