HDA7 Inhibitors

Chemical inhibitors of HDA7 employ various molecular mechanisms to impede its function. Trichostatin A, for instance, binds directly to the enzyme, thereby increasing the acetylation levels of histones and preventing the enzyme from exerting its gene silencing effects. Similarly, Suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, targets the catalytic site of HDA7, obstructing its ability to remove acetyl groups from histones. This action results in an open chromatin structure conducive to gene expression. Another inhibitor, Valproic acid, competes with acetyl-coenzyme A at the catalytic domain of HDA7, leading to hyperacetylation of histones. Sodium butyrate also interacts with the catalytic site of HDA7, which leads to a transcriptionally active chromatin configuration.

Entinostat, a benzamide histone deacetylase inhibitor, selectively binds to HDA7, while Romidepsin, a cyclic peptide, chelates the Zn2+ ion in the active site of HDA7, essential for its activity. Panobinostat, a broad-spectrum HDAC inhibitor, non-selectively binds to HDA7 among other HDACs, inhibiting their deacetylase activity. Belinostat, another hydroxamate-type inhibitor, targets multiple HDAC enzymes including HDA7 by binding to their zinc-binding domains. Chidamide, a selective class I HDAC inhibitor, binds to the enzyme's active site and impedes its function. Mocetinostat, which inhibits class I and IV HDACs, exerts its effect by binding to HDA7, leading to an increase in histone acetylation. Givinostat, similar to other hydroxamate-based inhibitors, interacts with the catalytic domain of HDA7, while Tacedinaline, an acetamide derivative, inhibits HDA7 by binding to its catalytic site. These interactions between chemical inhibitors and HDA7 culminate in the inhibition of the enzyme's ability to deacetylate histone proteins, thus affecting the chromatin structure.