Structural Basis for the Catalysis and Inhibition of Human Steroid 5α-Reductase 2

    May 2021 in “ The FASEB Journal ”
    Cheng Zhang, Zhiyi Wei
    Image of study
    TLDR The research gives new understanding on how human steroid 5α-reductases work and how drugs like finasteride inhibit them, which could help in creating new drugs.
    The study provides new insights into the structure and function of human steroid 5α-reductases (SRD5As), specifically SRD5A2, an enzyme that converts testosterone to dihydrotestosterone. Mutations in the SRD5A2 gene have been associated with 5α-reductase deficiency and prostate cancer. The drugs finasteride and dutasteride, which inhibit SRD5A2, are used to treat benign prostate hyperplasia and androgenic alopecia, and have also been indicated for COVID-19 treatment. The researchers solved a crystal structure of human SRD5A2 at 2.8 Å with finasteride, revealing a unique structural topology of 7-transmembrane helices and an intermediate adduct of finasteride and NADPH. The study also identified molecular mechanisms for the 5α-reduction of testosterone and the semi-irreversible finasteride inhibition involving residues E57 and Y91 of SRD5A2. These findings could facilitate drug development.
    Discuss this study in the Community →

    Related Community Posts Join

    6 / 503 results

      community DHT and 5AR respect post, it's importance within the brain

      in Research/Science  111 upvotes 9 months ago
      The conversation discusses whether to use finasteride for hair loss, considering its role in inhibiting DHT and 5AR, which can affect brain function and mood. Some users report anxiety and depression from finasteride, while others do not experience these side effects and emphasize the importance of DHT for brain and prostate health.

      community Why does it seem everyone favors finasteride over dutasteride?

      in Female  62 upvotes 7 months ago
      The conversation discusses preferences for hair loss treatments, specifically finasteride over dutasteride. Users share personal experiences, cost considerations, FDA approval status, and potential side effects, with some switching between treatments to find what works best for them.

      community Detailed 6 months update for FUE HT and 4 years of FIN-MIN journey

      in Progress Pictures  194 upvotes 1 year ago
      A 25-year-old who has been using minoxidil and finasteride for 4 years to treat hair loss, underwent a successful FUE hair transplant in Mumbai, India, in April 2023. The user reported positive results, including increased hair density and reduced frizziness, and plans to continue treatment for further growth.
      FCE 28260: A Forgotten 5α-Reductase Inhibitor

      community FCE 28260: A Forgotten 5α-Reductase Inhibitor

      in Research  330 upvotes 4 months ago
      FCE 28260 (PNU 156765), an under-explored 5α-reductase inhibitor, showcases promising results in research by Giudici et al., outperforming well-known treatments like Finasteride in reducing the conversion of testosterone to DHT. Its superior efficacy, demonstrated through lower IC50 values in both natural and human recombinant enzyme studies, suggests it could offer more effective management of DHT-related conditions. Additionally, its lower molecular weight hints at better potential for topical application, potentially offering advantages in treating conditions such as androgenic alopecia. Despite its potential, it has not advanced in development, possibly due to financial limitations, leaving its therapeutic prospects and side effect profile largely unexplored.

    Related Research

    2 / 2 results