KZR-4152

KZR-4152 is a small molecule inhibitor of the Sec61 translocon, the primary channel responsible for the translocation of secreted and transmembrane proteins into the endoplasmic reticulum (ER). Developed by Kezar Life Sciences, KZR-4152 was identified as an initial hit in a screening campaign for Sec61-dependent protein secretion inhibitors. Although it successfully blocked the secretion of several target proteins, it did not demonstrate significant anti-tumor activity in cell viability assays. Consequently, it served as a chemical starting point for a medicinal chemistry optimization program that led to the discovery of KZR-8834, a significantly more potent analog with robust anti-tumor properties.