BAY 1217389 demonstrates moderate efficacy as a monotherapy in tumor xenograft studies. However, when combined with paclitaxel, low doses of the Mps1 inhibitor reduce paclitaxel-induced mitotic arrest by weakening spindle assembly checkpoint (SAC) activity. Consequently, combination therapy significantly enhances efficacy compared to either paclitaxel or Mps1 inhibitor alone at their respective maximum tolerated doses (MTDs) across a wide range of xenograft models, including those exhibiting acquired or intrinsic paclitaxel resistance. Importantly, BAY 1217389 exhibits good tolerability without increasing toxicity when used in combination with paclitaxel monotherapy^[1].

BAY 1217389 inhibits Mps1 kinase activity with an IC50 value below 10 nM and demonstrates excellent selectivity. In cellular mechanistic assays, BAY 1217389 disrupts nocodazole-induced spindle assembly checkpoint (SAC) activity and triggers premature exit from mitosis, leading to multinuclearity and tumor cell death. Moreover, BAY 1217389 efficiently suppresses tumor cell proliferation in vitro^[1].