KZR-834

KZR-834 is a novel small molecule inhibitor of the Sec61 translocon, developed by Kezar Life Sciences. It functions by directly binding to the Sec61 channel, which is the primary portal for the entry of secreted and transmembrane proteins into the endoplasmic reticulum. By inhibiting the biogenesis of a specific subset of Sec61 client proteins—including immune checkpoints, VEGF-A, VEGFR, and EGFR—KZR-834 exerts broad anti-cancer and immunomodulatory effects. Preclinical studies have demonstrated its efficacy across various solid and hematologic malignancies, such as colorectal, pancreatic, and head and neck cancers, as well as lymphoma and myeloma. While KZR-834 showed significant preclinical potential and synergistic activity with anti-PD-1 therapies, Kezar Life Sciences prioritized the related compound KZR-261 for clinical development.