Lysine-specific demethylase 1 (LSD1) is a key epigeneticregulatorthat dimethylates H3K4 and is linked to prostate cancer. LSD1 was targeted by rhodium­(III) complex 4 featuring 4-chloro-2-phenylquinoline C∧N ligands and a 4,4′-dimethoxy-2,2′-bipyridine N∧N ligand (Figure C). Structural optimizationrevealed that chlorination of the C∧N ligand (complex 4) enhanced LSD1 inhibition (over 10 times greater than thatof the dechlorinated analogue complex), likely due to improved hydrophobicand electronic interactions with the catalytic pocket. This evidence concerns the gene KDM1A and prostate carcinoma.