BAY-1816032 is a potent and oral available BUB1 (budding uninhibited by benzimidazoles 1) kinase inhibitor with an IC50 of 7 nM.
BAY 1816032 is an orally active, ATP-competitive (Ki = 1.2 μM), highly potent and selective BUB1 inhibitor (IC50 = 6.1 nM with 10 μM ATP; affinity Kd = 3.3 nM/BUB1 vs 57 nM/STK10, 850 nM/DMPK2, 2.3 μM/DDR1 and >2.3 μM toward more than 390 other kinases) th at effectively targets BUB1-dependent cellular signaling (H2A-pThr120 IC50 = 29 nM post 1h treatment of nocodazole-arrested HeLa cells) and tumor cell proliferation in vitro (IC50 range from 0.5 to 5.8 μM in 43 human and mouse cancer cultures) and in human triple-negative breast xenograft models in vivo (25-50 mg/kg twice daily p.o.; SUM-149 and MDA-MB-436).
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].
[1] Siemeister G, et al. BAY 1816032, a novel BUB1 kinase inhibitor with potent antitumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Ishington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 287. doi:10.1158/1538-7445.AM2017-287
