BAY-1816032

BAY-1816032 is a potent and oral available BUB1 (budding uninhibited by benzimidazoles 1) kinase inhibitor with an IC₅₀ of 7 nM. IC50 & Target: IC50: 7 nM (BUB1)^[1] In Vitro: BAY-1816032 inhibits BUB1 enzymatic activity with an IC₅₀ of 7 nM, shows slow dissociation kinetics resulting in a long target residence time of 87 min, and an excellent selectivity on a panel of 395 kinases. Mechanistically BAY-1816032 abrogates nocodazole-induced Thr-120 phosphorylation of the major BUB1 target protein histone H2A in HeLa cells with an IC₅₀ of 29 nM, induced lagging chromosomes and mitotic delay. Persistent lagging chromosomes and missegregation are observed upon combination with low concentrations of paclitaxel. Single agent BAY-1816032 inhibits proliferation of various tumor cell lines with a median IC₅₀ of 1.4 μM and demonstrates synergy or additivity with paclitaxel or docetaxel in almost all cell lines evaluated (minimal combination index 0.3)^[1]. In Vivo: In tumor xenograft studies BAY 1816032 only marginally inhibits tumor growth as single agent upon oral administration, however, upon combination with paclitaxel or docetaxel a strong and statistically significant reduction of tumor size as compared to the respective monotherapy is observed^[1].