Multiple myeloma arises through the uncontrolled division of B cells, immune cells that specialize in antibody production. The secretory capacity of B cells is sustained by expansion of the endoplasmic reticulum (ER), a cellular compartment where secreted proteins are made. Secretory cells depend for their survival on a signaling pathway called the ER stress response, which expands the ER in response to increased demand. We have identified chemical inhibitors of Ire1, a core component of the ER stress response. We hypothesize that treatment of multiple myeloma cells with these inhibitors will block antibody secretion and cause the selective killing of malignant B cells.