BAZ2B Inhibitors

Chemical inhibitors of BAZ2B function through various mechanisms to impede its role in chromatin remodeling and recognition of methylated or acetylated histones. C646 acts by selectively inhibiting p300, a histone acetyltransferase that can acetylate BAZ2B, thereby reducing its ability to bind to nucleosomes effectively. Similarly, Garcinol and Anacardic Acid target p300 and PCAF, another histone acetyltransferase, which when inhibited, results in decreased acetylation of BAZ2B, limiting its chromatin-remodeling activity. Curcumin disrupts BAZ2B function by inhibiting the HAT activity of p300, which is essential for the acetylation and subsequent activation of BAZ2B. This disruption leads to a decrease in BAZ2B's capability to modulate chromatin structure.

Inhibitors like BIX-01294 and UNC0638 target the methylation recognition capacity of BAZ2B. BIX-01294 inhibits G9a HMTase, which methylates histone residues that BAZ2B recognizes and binds. UNC0638 further hinders BAZ2B function by inhibiting G9a and GLP histone methyltransferases, reducing BAZ2B's interaction with chromatin due to a decreased substrate for binding. Chaetocin and 3-Deazaneplanocin A also reduce histone methylation, with Chaetocin inhibiting SUV39H1 and 3-Deazaneplanocin A targeting EZH2, which in both cases would lead to a diminished ability of BAZ2B to bind its target methylated histones. Entinostat, a class I HDAC inhibitor, increases histone acetylation, possibly interfering with BAZ2B's interaction with methylated histones. Quercetin inhibits kinases that are responsible for BAZ2B phosphorylation, which is necessary for its activity, thereby indirectly reducing its function. MG-132 prevents the proteasomal degradation of proteins, which could interfere with ubiquitin-dependent signaling necessary for BAZ2B's activity. Finally, I-CBP112 competes with BAZ2B for binding to acetylated lysines on histones due to its inhibition of the bromodomains of CBP/p300, impeding BAZ2B's chromatin binding and subsequent function.