EN460

EN460 is a selective small-molecule inhibitor of Endoplasmic Reticulum Oxidoreductase 1 alpha (ERO1L, also known as ERO1A). ERO1L is an enzyme located in the endoplasmic reticulum (ER) that plays a critical role in the formation of disulfide bonds, which are essential for the proper folding of secretory and membrane proteins. By inhibiting ERO1L, EN460 disrupts protein folding homeostasis, leading to the accumulation of unfolded proteins and the subsequent induction of ER stress. This triggers the unfolded protein response (UPR) and can lead to apoptosis, particularly in cells with high secretory demands such as multiple myeloma plasma cells. EN460 was originally identified as a tool compound to study ER redox homeostasis and has since been investigated in preclinical models for its potential therapeutic application in multiple myeloma and other cancers where ERO1L is overexpressed.