2026/01/14 by K. Li, Jibira Yakubu Yakubu, Flemming Steen Jørgensen +1 · 1 voice
Medicine · Pharmacology, Toxicology and Pharmaceutics · #Hormonal Regulation and Hypertension #Pharmacogenetics and Drug Metabolism #Traditional Chinese Medicine Analysis
paper · pdf · doi:10.3390/biom16010144
openalex created_date 2026/01/14 · openalex publication_date 2026/01/14 · openalex updated_date 2026/07/31
Selective inhibition of CYP17A1 17,20-lyase is critical for treating hyperandrogenic disorders without the cortisol-depleting side effects of non-selective drugs like abiraterone. We evaluated tanshinones from Salvia miltiorrhiza as potential selective inhibitors using biochemical assays and computational modeling. Dihydrotanshinone (DT) emerged as the superior candidate; at 10 µM, it inhibited 17,20-lyase activity by 56.6% while preserving >93% of 17α-hydroxylase activity. This yields a selectivity index of 8.67, drastically outperforming abiraterone (0.73). Furthermore, DT displayed minimal off-target inhibition of CYP21A2 (14.9%) compared to abiraterone (29.8%). Molecular modeling suggests DT’s efficacy arises from a unique, functionally disruptive binding pose rather than superior thermodynamic affinity. Consequently, DT is validated as a potent natural product lead. Its dual selectivity over 17α-hydroxylase and CYP21A2 establishes the tanshinone scaffold as a promising candidate for developing safer therapies that suppress androgens while sparing cortisol biosynthesis.