Potent inhibitors of equine steroid isomerase EcaGST A3-3.
Authors: Lindström Helena, Mazari Aslam M A, Musdal Yaman, Mannervik Bengt
Journal: PloS one
Summary
# Editorial Summary: Potent Inhibitors of Equine Steroid Isomerase EcaGST A3-3 Equine glutathione transferase A3-3 (EcaGST A3-3) is a detoxication enzyme with an unusual dual function—it also catalyses steroid double-bond isomerisation more efficiently than any known mammalian enzyme, making it a particularly relevant research target given that horses share the steroidogenic pathway with humans. Lindström and colleagues screened 1,040 FDA-approved drugs to identify inhibitors of this enzyme, isolating 16 compounds that achieved at least 50% inhibition at 10 µM concentration. Four compounds—anthralin, sennoside A, tannic acid, and ethacrynic acid—demonstrated potent inhibitory effects, with IC50 values in the submicromolar range when tested against the natural substrate Δ5-androstene-3,17-dione. Whilst the translational applications remain early-stage, inhibition of steroid isomerase activity could offer therapeutic potential for managing steroid-hormone-dependent conditions in equine practice. These findings warrant further investigation into both the efficacy and safety profile of these compounds in vivo, particularly given the metabolic significance of steroid metabolism in horses.
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Practical Takeaways
- •This is fundamental research with potential future applications in treating steroid-hormone-dependent conditions in horses, but has no immediate clinical application for practising farriers or equine professionals
- •The findings validate the horse as a suitable research model for human steroid hormone biology, which may inform future therapeutic development
- •Results are enzyme-level in vitro work and would require substantial further development before any clinical use could be considered
Key Findings
- •EcaGST A3-3 is the most efficient steroid double-bond isomerase known in mammals
- •16 out of 1040 FDA-approved drugs screened showed at least 50% inhibition of EcaGST A3-3 at 10 μM concentration
- •Four compounds (anthralin, sennoside A, tannic acid, ethacrynic acid) demonstrated submicromolar IC50 values against the enzyme
- •Equine steroidogenic pathways are sufficiently similar to human pathways to support use of horses as animal models for steroid hormone research