Identification of Xenobiotics Interfering with 5α-Reductase (SRD5A2) Activity

This study developed an in silico/in vitro approach to identify potential inhibitors of the steroid 5α-reductase (SRD5A2) enzyme, which is crucial for male sexual development. Using molecular dynamics simulations and consensus docking, the researchers screened compounds from various databases. The androgen receptor modulator MK-0773 was identified as a moderate SRD5A2 inhibitor with an IC₅₀ value of 1.70 ±0.54μM. Unlike finasteride, MK-0773 does not act as a covalent inhibitor. These findings enhance the understanding of SRD5A2-ligand interactions and demonstrate the utility of the approach for identifying new SRD5A2 inhibitors.