KPT-251

KPT-251 is an orally bioavailable **small molecule** that acts as a **Selective Inhibitor of Nuclear Export (SINE)** targeting exportin 1 (XPO1), also known as CRM1. By binding to the NES-binding groove of XPO1/CRM1, KPT-251 blocks the export of key tumor suppressors and growth regulators from the nucleus, resulting in their nuclear retention. This leads to apoptosis and cell cycle arrest in cancer cells, particularly in hematologic and solid malignancies including acute myeloid leukemia (AML), diffuse malignant peritoneal mesothelioma (DMPM), glioblastoma (GBM), renal cell carcinoma (RCC), and chronic lymphocytic leukemia (CLL)[1][2][3][4][7][10]. KPT-251 has demonstrated preclinical antitumor efficacy with potent tumor growth inhibition, strong induction of apoptosis, and negligible toxicity to normal hematopoietic cells in various animal models. Its developer is Karyopharm Therapeutics[1][2][10].