MAD2L1 is a core component of the SAC, which monitors proper chromosome‐spindle microtubule attachment during cell division and ensures accurate sister chromatid segregation.[41] Accumulating evidence indicates that MAD2L1 overexpression is closely associated with tumorigenesis and progression in diverse malignancies, including hepatocellular carcinoma, cholangiocarcinoma, colorectal cancer, prostate cancer, and lung cancer.[42, 43] Our study identifies A2 as a potent MAD2L1 inhibitor and provides its first comprehensive preclinical evaluation as a targeted therapeutic. Here, MAD2L1 is linked to prostate cancer.