Mechanism Of Action :
In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c‐myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro‐apoptotic activity in vitro in multiple myeloma cells and showed anti‐tumor activity in murine xenograft models of multiple myeloma and diffuse large B cell lymphoma. The combination of selinexor and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and increased anti‐tumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.
