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Herein we report an unprecedented off\u2010target interaction between abiraterone and oncogenic hedgehog proteins. Our experiments indicate that abiraterone and its structural congener, galeterone, can replace cholesterol as a substrate in a specialized biosynthetic event of hedgehog proteins, known as cholesterolysis. The off\u2010target reaction generates covalent hedgehog\u2013drug conjugates. Cell\u2010based reporter assays indicate that these conjugates activate hedgehog signaling when present in the low nanomolar range. Because hedgehog signaling is implicated in prostate cancer progression, and abiraterone is administered to treat advanced stages of the disease, this off\u2010target interaction may have therapeutic significance.<\/jats:p>","DOI":"10.1002\/cmdc.201600238","type":"journal-article","created":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T03:52:39Z","timestamp":1468986759000},"page":"1983-1986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hedgehog Proteins Consume Steroidal CYP17A1 Antagonists: Potential Therapeutic Significance in Advanced Prostate Cancer"],"prefix":"10.1002","volume":"11","author":[{"given":"Brandon M.","family":"Bordeau","sequence":"first","affiliation":[{"name":"Chemistry Department State University of New York at Binghamton  4400 Vestal Parkway East Binghamton NY 13902 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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