{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:03Z","timestamp":1787027643988,"version":"build-2736575974"},"reference-count":100,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CANCER RESEARCH SWITZERLAND","award":["KFS-5557-02-2022"],"award-info":[{"award-number":["KFS-5557-02-2022"]}]},{"name":"SWISS GOVERNMENT EXCELLENCE SCHOLARSHIP","award":["2022.0470"],"award-info":[{"award-number":["2022.0470"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 \u00b5M, it inhibited 17,20-lyase activity by 56.6% while preserving &gt;93% of 17\u03b1-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\u2019s 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 17\u03b1-hydroxylase and CYP21A2 establishes the tanshinone scaffold as a promising candidate for developing safer therapies that suppress androgens while sparing cortisol biosynthesis.<\/jats:p>","DOI":"10.3390\/biom16010144","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:03:10Z","timestamp":1768381390000},"page":"144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dihydrotanshinone as a Natural Product-Based CYP17A1 Lyase Inhibitor for Hyperandrogenic Disorders"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3048-1864","authenticated-orcid":false,"given":"Kaige","family":"Li","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, CH-3010 Bern, Switzerland"},{"name":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, CH-3010 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7637-0559","authenticated-orcid":false,"given":"Jibira","family":"Yakubu","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, CH-3010 Bern, Switzerland"},{"name":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, CH-3010 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-2998","authenticated-orcid":false,"given":"Flemming Steen","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8331-5902","authenticated-orcid":false,"given":"Amit V.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, University Children\u2019s Hospital, Inselspital, CH-3010 Bern, Switzerland"},{"name":"Translational Hormone Research Program, Department of Biomedical Research, Faculty of Medicine, University of Bern, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1759","DOI":"10.1210\/clinem\/dgaf037","article-title":"Population-Based vs Health System and Insurer Records: Significant Underdiagnosis of PCOS","volume":"110","author":"Hatoum","year":"2025","journal-title":"J. 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