CSN7a Inhibitors

The chemical class of CSN7a Inhibitors refers to a group of compounds that indirectly influence the activity of the COP9 signalosome subunit 7a, primarily through their actions on the ubiquitin-proteasome system (UPS). CSN7a is a regulatory component of the COP9 signalosome, which plays a role in deneddylation, a process that removes the NEDD8 modification from cullins, thereby regulating the activity of cullin-RING ligases (CRLs). These ligases are essential for the ubiquitination of proteins, marking them for degradation by the proteasome. The inhibitors listed are primarily proteasome inhibitors, which by their nature, lead to an accumulation of ubiquitinated proteins within the cell. This accumulation can create a feedback loop affecting various signaling pathways and cellular processes, including those that involve CSN7a.

The proteasome inhibitors MG132, Bortezomib, Lactacystin, PI-1840, Curcumin, Epoxomicin, Carfilzomib, Withaferin A, Oprozomib, Velcade, Celastrol, and Disulfiram act by binding to the proteasomal subunits responsible for protein degradation. This binding prevents the proteasome from performing its function, leading to increased levels of ubiquitinated proteins. The accumulation of these proteins can, in turn, lead to the sequestration of CSN7a and other COP9 signalosome components, as they are recruited to manage the excess of ubiquitinated substrates. This sequestration can impede the normal function of CSN7a in the COP9 signalosome complex.