Here, based on the optimal scaffolds of epitope peptides and advanced in silico approaches, we developed ST‐CY14 as a high‐potency PPI peptide inhibitor that effectively blocks the Nur77‐PPARγ interaction both in vitro and in vivo, which not only validates the feasibility of exploiting the Nur77‐PPARγ interaction as a target of breast cancer for drug discovery, but also provides an effective paradigm for computer‐aided drug design in PPI‐peptide‐inhibitor research. This evidence concerns the gene NR4A1 and breast cancer.