INO80B Inhibitors

Chemical inhibitors of INO80B encompass a variety of compounds that interfere with its role in chromatin remodeling. Trichostatin A, for instance, works by inhibiting histone deacetylases, which results in the maintenance of acetylated histones. This alteration in histone acetylation status can prevent INO80B from effectively modifying the chromatin structure. Similarly, chloroquine's ability to intercalate into DNA and RNA poses a structural hindrance for DNA-dependent enzymes like INO80B, limiting its interaction with the chromatin substrate. Compounds such as Nocodazole, which impedes microtubule polymerization, affect INO80B indirectly due to the protein's involvement in chromosomal segregation during mitosis-a process that is microtubule-dependent.

Further, the inhibition of cyclin-dependent kinases by DRB, which is crucial for cell cycle progression, may indirectly restrict INO80B's chromatin remodeling activity that is tied to the cell cycle. Etoposide and Camptothecin, which stabilize DNA-topoisomerase complexes, result in DNA breaks and, consequently, an engagement of the cellular repair machinery. This engagement can lead to an indirect inhibition of INO80B's chromatin remodeling functions. Meanwhile, Mimosine and Aphidicolin can bring about a cessation of DNA replication, a phase where INO80B is actively involved, thereby indirectly limiting its activity. Caffeine inhibits DNA repair enzymes, potentially restricting the DNA repair pathways where INO80B operates. Rocaglamide's inhibition of translation initiation can also limit the availability of essential proteins required for INO80B's function. Lastly, MG132, by inhibiting the proteasome, can disrupt the cycling and supply of histones critical for INO80B-mediated chromatin remodeling, implying another indirect method of inhibition. Each of these compounds, through their distinct mechanisms, can influence the ability of INO80B to carry out its role in modifying chromatin structure and function.