Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target

Finasteride, a 5-alpha reductase (5α-R) inhibitor, is widely used drug for treating androgen-dependent conditions. However, its use associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, multidisciplinary approach has been identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of on phenylethanolamine N-methyltransferase (PNMT), the limiting enzyme formation stress hormone epinephrine. The interaction PNMT was supported by docking molecular dynamics analysis vitro assay, confirming nature binding. Finally, this inhibition also confirmed vivo rat model. Literature data indicate perturbation correlated sexual psychological side effects. Therefore, results here obtained suggest binding might have role producing effects exerted treatment.