BAY 1816032

BAY 1816032 is a highly potent and selective small molecule inhibitor of BUB1 (budding uninhibited by benzimidazoles 1) kinase, with an IC50 of approximately 7 nM. It was developed as the first orally bioavailable BUB1 kinase inhibitor and demonstrates high selectivity within the kinome. BUB1 is a mitotic checkpoint serine/threonine kinase involved in chromosome arm resolution and correction of spindle attachment errors during cell division. Inhibition of BUB1 by BAY 1816032 disrupts these processes, leading to chromosome mis-segregation and increased sensitivity of tumor cells to chemotherapeutic agents such as taxanes (paclitaxel, docetaxel), ATR inhibitors, and PARP inhibitors. Preclinical studies showed that combining BAY 1816032 with paclitaxel or olaparib resulted in significant tumor growth reduction in triple-negative breast cancer xenograft models compared to monotherapies. The compound was developed by Bayer Pharma for potential use in cancer therapy but its development has been discontinued at the preclinical stage[2][3][5][6][8].