KPT-205

KPT-205 is a small molecule selective inhibitor of nuclear export (SINE) developed by Karyopharm Therapeutics. It functions by irreversibly binding to and inhibiting CRM1 (Exportin-1), a nuclear export protein encoded by the XPO1 gene. CRM1 is responsible for the transport of tumor suppressor proteins (TSPs) out of the nucleus; by inhibiting this process, KPT-205 causes the nuclear retention and activation of TSPs such as p53, p27, and PAR-4, leading to selective apoptosis in cancer cells. In preclinical studies, KPT-205 has demonstrated growth inhibition and pro-apoptotic activity in pancreatic cancer cell lines and other solid tumor models.