In vitro activity: M2I-1 (full name: Mad2 Inhibitor-1) is a first-in-class small molecule inhibitor that targets the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the mitotic SAC (spindle assembly checkpoint). It can disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. It can also inhibited the Mad2-F-Mbp1 interaction in FP assays. Based on computational and biochemical analyses, M2I-1 was found to disturb conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells. Thus, this study identifies the SAC specific complex formation between Mad2 and Cdc20 as a protein-protein interaction that can be targeted by small molecules.

Kinase Assay: M2I-1 (full name: Mad2 Inhibitor-1) is a first-in-class small molecule inhibitor that targets the binding of Mad2 to Cdc20, an essential protein-protein interaction (PPI) within the mitotic SAC (spindle assembly checkpoint). It can disturbs conformational dynamics of Mad2 critical for complex formation with Cdc20. It can also inhibited the Mad2-F-Mbp1 interaction in FP assays.

Cell Assay: Based on computational and biochemical analyses, M2I-1 was found to disturb conformational dynamics of Mad2 critical for complex formation with Cdc20. Cellular studies revealed that M2I-1 weakens the SAC response, indicating that the compound might be active in cells.