CRBN Inhibitors

CRBN inhibitors encompass a group of compounds that modulate the activity of the protein cereblon, either through direct interaction or by influencing the cellular pathways in which CRBN is involved. CRBN is a substrate receptor for the CRL4 E3 ubiquitin ligase complex, which is critical for the ubiquitination and subsequent proteasomal degradation of target proteins. Compounds like lenalidomide, pomalidomide, and thalidomide are known to bind directly to CRBN, affecting its ability to recruit specific substrates for ubiquitination. This modulation of substrate specificity has a profound effect on the protein turnover within the cell and consequently on various cellular processes.

Proteasome inhibitors like bortezomib, carfilzomib, and ixazomib can also indirectly influence CRBN's function. By preventing the degradation of ubiquitinated proteins, these compounds can lead to the accumulation of these proteins within the cell, which could alter the functional dynamics of CRBN in the ubiquitin-proteasome system. Additionally, compounds like MG-132 exhibit reversible inhibition of the proteasome, offering a different approach to modulating CRBN activity by stabilizing its substrates. Other chemicals, such as all-trans retinoic acid, chloroquine, and hydroxychloroquine, do not interact directly with CRBN but can impact cellular differentiation, proliferation, and lysosomal function, respectively. This can lead to changes in the cellular environment that indirectly affect CRBN's role. MLWhile there are no known chemicals that directly inhibit the Cereblon (CRBN) protein, various compounds target pathways or processes in which CRBN is involved. CRBN is a part of the E3 ubiquitin ligase complex and plays a role in the ubiquitin-proteasome system (UPS), a critical pathway for protein degradation.