Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target
Silvia Giatti, Alessandro Di Domizio, Silvia Diviccaro, Eva Falvo, Donatella Caruso, Alessandro Contini, Roberto Cosimo Melcangi
Journal of Medicinal Chemistry2021
Summary (paraphrased)
Reasoning that finasteride's sexual, psychological, and physical complaints may involve actions beyond 5-alpha-reductase inhibition, the Melcangi group ran a proteome-wide computational screen for additional finasteride binding partners. The screen flagged phenylethanolamine N-methyltransferase (PNMT) — the rate-limiting enzyme in epinephrine (adrenaline) synthesis — as a plausible off-target, a prediction supported by molecular docking. The finding opens a non-androgenic mechanistic route (stress-hormone dysregulation) for finasteride's systemic effects.
Why it’s in the corpus
Identifies a novel non-5AR finasteride target in the adrenaline-synthesis pathway — a genuinely new mechanistic hypothesis for systemic PFS symptoms, from the core neurosteroid group.