OTC Inhibitors

The inhibitors of the Ovarian Tumour Domain Containing (OTC) protease predominantly function by indirectly affecting the protein's ubiquitination and neddylation processes. The ubiquitin-proteasome system (UPS) is a key cellular mechanism for protein degradation and regulation, where OTC plays a crucial role. Inhibitors like MLN4924 and Pevonedistat target the NEDD8-activating enzyme, a critical component of the neddylation pathway, which is essential for the activation of cullin-RING ligases (CRLs). These CRLs are vital for the ubiquitination of specific substrates, including those involved in cell cycle regulation and signal transduction. By inhibiting neddylation, these chemicals effectively reduce the functional activity of OTC.

Other inhibitors, such as MG132, Bortezomib, Carfilzomib, and Marizomib, are proteasome inhibitors. The proteasome is the final step in the UPS where proteins tagged for degradation by ubiquitination are broken down. By inhibiting the proteasome, these chemicals cause an accumulation of ubiquitinated proteins, indirectly influencing OTC's regulatory role in protein turnover. Additionally, compounds like Thalidomide and Lenalidomide modulate the activity of ubiquitin ligases, thereby altering the ubiquitination landscape in the cell and indirectly impacting OTC function.