HCI-2389

HCI-2389 is a small molecule, irreversible inhibitor of Never in mitosis gene A-related kinase 2 (Nek2). Developed by researchers at the Huntsman Cancer Institute, it was designed to address resistance to proteasome inhibitors like bortezomib in multiple myeloma. Nek2 is a serine/threonine kinase associated with centrosome function and cell cycle progression, and its overexpression correlates with increased proteasome activity and drug resistance. By inhibiting Nek2, HCI-2389 reduces proteasome function, increases levels of cyclin B1 and cdc2, and induces cell cycle arrest in the G2/M phase. Preclinical studies have demonstrated its efficacy in multiple myeloma, lung cancer, and Leydig tumor cell lines.