TRIM65 Inhibitors

MG132 is a peptide aldehyde that inhibits proteasome activity. TRIM65 functions as an E3 ubiquitin ligase, and inhibition of the proteasome with MG132 would lead to an accumulation of TRIM65's ubiquitination substrates, therefore functionally inhibiting TRIM65's role in protein turnover.

Lactacystin is a natural product that irreversibly binds to and inhibits the proteasomal subunits. This would inhibit the degradation of ubiquitinated proteins by the proteasome, which is the downstream effect of TRIM65's ubiquitin ligase activity, thus indirectly inhibiting TRIM65 function.

Epoxomicin is a selective proteasome inhibitor that covalently binds to the 20S proteasome. By preventing the proteasomal degradation of ubiquitinated proteins, Epoxomicin would functionally inhibit the protein turnover mediated by TRIM65.

Bortezomib is a dipeptidyl boronic acid that inhibits the 26S proteasome. This inhibition results in the buildup of proteins ubiquitinated by TRIM65, which would otherwise be degraded, thus functionally inhibiting TRIM65's role in proteostasis.

MLN4924 inhibits NEDD8 activating enzyme, which is required for neddylation that activates E3 ubiquitin ligases like TRIM65. Inhibition of this enzyme would disrupt TRIM65's ability to ubiquitinate target proteins, thus directly inhibiting its function.

Oprozomib is an oral proteasome inhibitor that would block the degradation of TRIM65 target proteins in the ubiquitin-proteasome pathway, leading to functional inhibition of TRIM65's E3 ligase activity.

Carfilzomib is an irreversible proteasome inhibitor. By blocking proteasomal degradation, it would lead to the accumulation of proteins that TRIM65 has tagged for degradation, functionally inhibiting TRIM65's role in the cell.

Withaferin A is known to inhibit the proteasomal activity. It would, therefore, lead to an accumulation of ubiquitinated proteins by TRIM65, functionally inhibiting its regulatory role in protein degradation.

Chloroquine increases lysosomal pH, which could interfere with the degradation of proteins ubiquitinated by TRIM65, leading to a functional inhibition of TRIM65's role in lysosome-mediated degradation.

Concanamycin A is a specific inhibitor of V-ATPases which are essential for lysosomal acidification. By inhibiting V-ATPases, it could functionally inhibit the degradation of proteins that are targeted by TRIM65 for lysosomal degradation.