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

    February 2026 in “ Toxicology Letters
    Jacek Kędzierski, Rianne E van Diest, Julien Arthur Allard, Andreas M. Erharter, Alex Odermatt, Martin Smieko
    TLDR MK-0773 is a moderate inhibitor of the SRD5A2 enzyme.
    The study used an in silico/in vitro approach to identify potential inhibitors of the steroid 5α-reductase (SRD5A2) enzyme, which is important for male sexual development. Through virtual screening of 7940 ligands, MK-0773 was identified as a moderate SRD5A2 inhibitor with an IC50 of 1.70 μM, similar in binding to finasteride but without forming a covalent bond with NADPH. The findings suggest MK-0773's potential as an SRD5A2 inhibitor, which could be beneficial for conditions like male pattern baldness and prostate issues. However, its efficacy in vivo remains uncertain, and the study highlights the limitations of the in silico screening strategy, suggesting future improvements for better understanding of ligand binding dynamics.
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