KPT-249

KPT-249 is a small-molecule Selective Inhibitor of Nuclear Export (SINE) developed by Karyopharm Therapeutics. It acts as a potent and selective antagonist of Exportin 1 (XPO1), also known as Chromosome Region Maintenance 1 (CRM1), which is the primary nuclear export protein for various tumor suppressor proteins, including p53, p21, and FOXO. By inhibiting XPO1, KPT-249 prevents the export of these proteins from the nucleus to the cytoplasm, leading to their nuclear accumulation and subsequent induction of cell cycle arrest and apoptosis in malignant cells. KPT-249 has been primarily studied in preclinical models of multiple myeloma, where it has demonstrated synergistic activity when combined with proteasome inhibitors such as bortezomib and carfilzomib.