4930524E20Rik Inhibitors

The chemical class designated as Ube2dnl2 Inhibitors encompasses a group of compounds that interact with the ubiquitin-proteasome system (UPS), a cellular pathway with a role in protein degradation and turnover, which indirectly affects the activity of ubiquitin-conjugating enzyme E2D N-terminal like 2 (UBE2DNL2). Within this class, PYR-41 is notable for its inhibition of the ubiquitin-activating enzyme E1, laying the groundwork for its indirect impact on UBE2DNL2 by impeding the initial activation step required for ubiquitin to attach to target proteins. Similarly, MLN4924, known as Pevonedistat, targets the NEDD8-activating enzyme, which is vital for the functioning of ubiquitin ligases, thereby altering the ubiquitination landscape that UBE2DNL2 is part of. Proteasome inhibitors, a prominent group within this chemical class, including Bortezomib, MG132, Clasto-lactacystin β-lactone, Epoxomicin, Lactacystin, and Withaferin A, operate by preventing the breakdown of proteins tagged for degradation by ubiquitin, thereby indirectly affecting the substrates and processes that UBE2DNL2 would typically engage with.

In addition to proteasome inhibitors, this class includes compounds such as IU1 and HBX 41,108, which modulate the activity of deubiquitinating enzymes like USP14 and USP7, respectively. By altering the balance of ubiquitination and deubiquitination, these inhibitors can affect the turnover and recycling of ubiquitin, which can influence the functional context within which UBE2DNL2 operates. Compounds like G5, which hinders the chaperone-mediated autophagy pathway, and Chloroquine, an agent that raises the lysosomal pH inhibiting lysosomal degradation, also form part of this chemical class. These compounds impact the cellular protein degradation pathways, which, while distinct from the proteasome, can impact overall protein turnover and ubiquitin dynamics, thereby exerting an indirect influence on UBE2DNL2 activity.