KPT-227

KPT-227 is a Selective Inhibitor of Nuclear Export (SINE) compound developed by Karyopharm Therapeutics. It acts as an irreversible inhibitor of Chromosome Region Maintenance 1 (CRM1), also known as Exportin-1 (XPO1), which is the major nuclear export receptor for tumor suppressor proteins (TSPs) such as p53, p27, and PAR-4. By blocking the export of these proteins from the nucleus to the cytoplasm, KPT-227 restores their normal regulatory functions, leading to selective apoptosis in cancer cells. Preclinical data in pancreatic cancer models demonstrated that KPT-227 induces growth inhibition and apoptosis at nanomolar concentrations while exhibiting minimal toxicity to normal cells.