Ataxin-7 Inhibitors

Ataxin-7 inhibitors encompass a class of compounds that serve to modulate the activity of Ataxin-7, a protein known to be involved in transcription regulation through its role in the SAGA complex. This modulation is achieved through the alteration of post-translational modifications, particularly acetylation and deacetylation, which are processes critical to the transcriptional regulation functions of Ataxin-7. The chemical inhibitors target enzymes such as sirtuins and histone deacetylases (HDACs) that regulate these post-translational modifications.

The compounds listed, such as Selisistat, Sirtinol, and EX-527, function primarily by inhibiting the activity of sirtuins, a family of deacetylases, thereby influencing the acetylation status of Ataxin-7. As sirtuins, particularly SIRT1, play a role in deacetylating histones and other proteins, their inhibition can result in increased acetylation levels. Increased acetylation can affect the interaction of Ataxin-7 with other components of the SAGA complex and the transcription machinery, thereby modulating its role in gene expression. Cambinol and Tenovin-6, which inhibit multiple sirtuins, can also lead to changes in the acetylation landscape within the cell, affecting Ataxin-7 indirectly. Other compounds such as Trichostatin A and Vorinostat belong to the class of HDAC inhibitors. By preventing deacetylation, these inhibitors cause an increase in the acetylation of histones, leading to a more open chromatin structure and an altered gene expression profile. The resultant hyperacetylated state can have various downstream effects on protein interactions and functions, including those involving Ataxin-7. The exact mechanism by which the altered gene expression influences Ataxin-7 activity is complex but is anchored in the principle that changes in chromatin structure and histone modification states are central to the regulation of transcription, where Ataxin-7 plays a crucial role.