ASXL3 Inhibitors

Chemical inhibitors of ASXL3 function by disrupting the interaction between ASXL3 and histone deacetylases (HDACs), which are crucial for the protein's role in chromatin remodeling and gene expression regulation. Trichostatin A, Vorinostat, Panobinostat, Romidepsin, MGCD0103, Belinostat, Entinostat, Tacedinaline, Valproic Acid, AR-42, Quisinostat, and CUDC-101 are all HDAC inhibitors that alter the acetylation status of histones. These changes in histone acetylation can impair the ability of ASXL3 to modulate chromatin structure effectively. For instance, Trichostatin A and Vorinostat can lead to increased histone acetylation, thus preventing ASXL3 from maintaining chromatin in a configuration that is conducive to its normal function. Panobinostat, as a pan-HDAC inhibitor, further broadens the scope of HDAC inhibition, impacting multiple classes of HDACs that ASXL3 might interact with, leading to a more generalized disruption of its function.

Similarly, Romidepsin's specificity for Class I HDACs can singularly affect the subset of HDACs that are most relevant for ASXL3's activity in certain contexts. MGCD0103 and Belinostat, by inhibiting Class I and IV HDACs, target the enzyme classes that directly interact with ASXL3, leading to a functional impairment of ASXL3's ability to regulate gene expression. Entinostat's selective inhibition of Class I HDACs and Tacedinaline's inhibition of HDACs can also disrupt ASXL3 function by a similar mechanism. Valproic Acid, with its HDAC inhibitory activity, changes histone acetylation states that are critical for ASXL3's role in gene regulation. AR-42 and Quisinostat, by inhibiting HDACs, can disrupt the chromatin remodeling activities of ASXL3, affecting its ability to regulate gene expression. Lastly, CUDC-101's multi-target inhibition profile, including HDACs, suggests that it can impede ASXL3's chromatin-modifying activities, leading to a comprehensive inhibition of ASXL3's functional role within the cell.