TRIM64B Inhibitors

Chemical inhibitors of TRIM64B can interfere with the protein's function in a variety of ways, primarily by targeting the proteasomal and lysosomal degradation pathways. Proteasome inhibitors such as MG132, Lactacystin, Epoxomicin, Bortezomib, and Withaferin A obstruct the proteasome's ability to degrade ubiquitinated proteins. Since TRIM64B is thought to be involved in tagging proteins for degradation, the accumulation of these proteins due to the inhibition of the proteasome can lead to an inhibition of TRIM64B function. This is because the normal cycle of tagging and degradation that TRIM64B is a part of is disrupted, leading to an accumulation of proteins that would otherwise be degraded.

Other compounds, such as MLN4924, disrupt processes that are upstream of TRIM64B's role in protein turnover. MLN4924 inhibits the NEDD8-activating enzyme, thus potentially affecting TRIM64B indirectly by altering the regulation of cullin-RING ubiquitin ligases (CRLs) that might be necessary for TRIM64B's function. Lysosomal function disruptors such as Chloroquine, Concanamycin A, Leupeptin, and Pepstatin A, impede different aspects of the lysosomal degradation pathway. Chloroquine and Concanamycin A disrupt lysosomal acidification, whereas Leupeptin and Pepstatin A inhibit lysosomal proteases. Since lysosomal function is crucial for the degradation of cellular components, inhibition of lysosomes can result in an inhibition of TRIM64B if it relies on this pathway. Lastly, O-phenanthroline disrupts metalloprotease activity, which could inhibit TRIM64B if its function is contingent upon metalloprotease-mediated processes. Eeyarestatin I specifically inhibits components of the ER-associated degradation pathway, which could affect TRIM64B if it is involved in this cellular mechanism.