MG-001

MG-001 is a small molecule inhibitor of the Sec61 translocon, the primary channel responsible for the translocation of proteins into the endoplasmic reticulum. Developed by Gate Bioscience, MG-001 is being investigated for the treatment of immunoglobulin light chain (AL) amyloidosis. The compound blocks the co-translational translocation of proteins, including misfolded immunoglobulin light chains (LCs), into the endoplasmic reticulum. In plasma cells, which have a high secretory demand, this inhibition leads to proteotoxic stress and apoptosis. Preclinical studies presented at ASH 2024 showed that MG-001 reduces the viability of AL amyloidosis cell lines and acts synergistically with the proteasome inhibitor bortezomib. Unlike some other compounds in the same class, MG-001 is a non-selective inhibitor of Sec61 clients.