Dysregulated androgen receptor (AR) signalling is a hallmark of advanced prostate cancer. This study showed that disrupting an interaction between the AR and a co-regulator protein could be beneficial. The authors structurally designed a peptidomimetic that disrupted the interaction between the scaffold protein PELP1 (proline-, glutamic acid- and leucine-rich protein 1) and the AR by targeting the LXXLLL motif. In cells, the compound prevented nuclear translocation of the AR and inhibited androgen-induced proliferation, and it inhibited tumour growth in a mouse xenograft model of prostate cancer.