EDEM3 Inhibitors

EDEM3 inhibitors, as a theoretical chemical class, would encompass compounds that either directly inhibit the mannose trimming activity of EDEM3 or modulate the ERAD pathway's capacity to handle misfolded glycoproteins. Since direct inhibition of EDEM3 has not been established, the chemicals listed are those that may influence the pathways and processes associated with EDEM3 function. Among the indirect inhibitors, kifunensine, swainsonine, castanospermine, and 1-deoxynojirimycin target different aspects of glycan processing. By inhibiting specific mannosidases or glucosidases, these compounds can alter glycoprotein maturation, thereby impacting the substrates that EDEM3 would typically recognize and process. This alteration can lead to an accumulation of misfolded proteins, challenging the ERAD pathway's capacity and indirectly influencing EDEM3 activity.

Proteostasis modulators like MG132 and eeyarestatin I can cause an accumulation of ubiquitinated proteins, exacerbating ER stress and indirectly increasing the burden on EDEM3's function within the ERAD pathway. Tunicamycin and brefeldin A disrupt protein glycosylation and trafficking between the ER and Golgi apparatus, respectively, which can lead to an increased load of misfolded proteins that would require EDEM3-mediated degradation. Inhibitors of EDEM3 would be compounds that can interfere with its function in the ERAD pathway, either by directly inhibiting its mannosidase-like activity or by influencing the degradation process of misfolded glycoproteins. However, given the lack of specific inhibitors, we can consider chemicals that influence the ERAD pathway or protein folding and degradation mechanisms in the endoplasmic reticulum (ER).