KPT-0127

KPT-0127 is a Selective Inhibitor of Nuclear Export (SINE) compound developed by Karyopharm Therapeutics. It functions by directly and covalently modifying and inhibiting Exportin 1 (XPO1/CRM1), a key nuclear export protein. By blocking CRM1-mediated export, KPT-0127 forces the nuclear accumulation and activation of various tumor suppressor proteins (TSPs) and growth regulatory proteins (GRPs), including p53, p21, FOXO, and IκB. This nuclear retention leads to cell cycle arrest at both the G1/S and G2/M phases and induces apoptosis specifically in malignant cells while sparing normal proliferating cells. Preclinical studies have demonstrated that KPT-0127 is well-tolerated in toxicology models and exhibits potent anti-tumor activity in xenograft models of multiple myeloma and colorectal cancer. It has been evaluated for oral, subcutaneous, and intravenous administration in early research settings.