BAY-1816032 is an inhibitor of the mitotic checkpoint serine/threonine protein kinase BUB1 (IC50 = 6.1 nM).1 It is selective for BUB1 over FLT3 (IC50 = 4.2 ?M) and 15 other kinases (IC50s = >10 ?M for all). BAY-1816032 inhibits proliferation of a variety of cancer cells (median IC50 = 1.4 ?M) and acts synergistically with the mitotic inhibitor paclitaxel to increase the rate of chromosomal segregation defects during mitosis in HeLa cells. It reduces tumor growth in a SUM149 mouse xenograft model when administered at a dose of 25 mg/kg and has an additive effect on reducing tumor growth when used in combination with paclitaxel in the same model.
1.Siemeister, G., Mengel, A., Fernández-Montalván, A.E., et al.Inhibition of BUB1 kinase by BAY 1816032 sensitizes tumor cells toward taxanes, ATR, and PARP inhibitors in vitro and in vivoClin. Cancer Res.25(4)1404-1414(2019)