In brief, serial structure–activity relationship studies led to the discovery of a GR antagonist similar in potency to mifepristone (IC50 = 5.6 ± 2.6 nmol/L for ORIC-101; IC50 = 3.3 ± 0.6 nmol/L for mifepristone in cancer cells) but with significantly reduced androgen receptor (AR) agonism and improved cytochrome P450 (CYP) inhibition profiles. This evidence concerns the gene AR and cancer.