{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:38Z","timestamp":1792003718984,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["Sonata 2020\/39\/D\/NZ7\/00572"],"award-info":[{"award-number":["Sonata 2020\/39\/D\/NZ7\/00572"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007364","name":"CRT Foundation","doi-asserted-by":"publisher","award":["OLIS_CRT_22_01"],"award-info":[{"award-number":["OLIS_CRT_22_01"]}],"id":[{"id":"10.13039\/100007364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>\n                    Castration\u2010resistant prostate cancer relies on intratumoral androgen synthesis mediated by cytochrome P450 17A1 (CYP17A1). Treatment with the only clinically used CYP17A1 inhibitor, abiraterone, is limited by resistance and side effects, underscoring the urgent need for new CYP17A1 inhibitors with greater selectivity and improved safety profiles. In response to this challenge, we designed, synthesized, and biologically evaluated 30 novel piperidine derivatives. All compounds were initially screened in the H295R cell line to assess their inhibitory activity toward both CYP17A1 and off\u2010target CYP21A2. Compounds were further evaluated in cell viability assays using prostate cancer cells and a normal prostate cell line. The most potent and selective compounds were subjected to further biological studies: IC\n                    <jats:sub>50<\/jats:sub>\n                    determination, steroid profiling, cell migration assay, aldo\u2013keto reductase family 1 member C3 inhibition assays, absorption, distribution, metabolism, and excretion prediction, and solubility testing. Several compounds emerged as the most active and selective leads, highlighting their potential for pharmaceutical development.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70336","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:01:03Z","timestamp":1791180063000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery and Characterization of Novel Piperidine Derivatives as Potent Cytochrome P450 17A1 Inhibitors for Prostate Cancer Therapy"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-5418","authenticated-orcid":false,"given":"Angelika","family":"Grudzi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances Medical University of Lublin  Lublin Poland"}],"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 University Children's Hospital Bern  Bern Switzerland"},{"name":"Translational Hormone Research Program, Department of Biomedical Research University of Bern  Bern Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-3162","authenticated-orcid":false,"given":"Chiara","family":"Vigato","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-0590","authenticated-orcid":false,"given":"Therina","family":"du Toit","sequence":"additional","affiliation":[{"name":"Translational Hormone Research Program, Department of Biomedical Research University of Bern  Bern Switzerland"},{"name":"Department of Nephrology and Hypertension University Hospital Bern Inselspital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Vanzetti","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rados\u0142aw","family":"Zan","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances Medical University of Lublin  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-4460","authenticated-orcid":false,"given":"Donatella","family":"Boschi","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-2127","authenticated-orcid":false,"given":"Simonetta","family":"Oliaro\u2010Bosso","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7018-8334","authenticated-orcid":false,"given":"Fredrik","family":"Bj\u00f6rkling","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology University of Copenhagen  Copenhagen Denmark"}],"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  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 University Children's Hospital Bern  Bern Switzerland"},{"name":"Translational Hormone Research Program, Department of Biomedical Research University of Bern  Bern Switzerland"},{"name":"Department of Digital Medicine University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-2522","authenticated-orcid":false,"given":"Tomasz M.","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Chemical Technology of Pharmaceutical Substances Medical University of Lublin  Lublin Poland"},{"name":"Department of Drug Design and Pharmacology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175730"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpuro1322"},{"key":"e_1_2_8_6_1","first-page":"365","article-title":"Mechanisms of Resistance in Castration\u2010Resistant Prostate Cancer (CRPC)","volume":"4","author":"Chandrasekar T.","year":"2015","journal-title":"Translational Andrology and Urology"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15205047"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2022.10.018"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.04.010"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06375"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414673200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11020037"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2014.tb00590.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111261"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0931"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00013a022"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014618"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9749"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.07.019"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.09.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14406"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17954"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0186"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.66"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2013.274"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2189"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2020.1785289"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00442"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2025.2463014"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b02138"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00939"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114366"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116193"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.4c00150"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.09.019"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc9800071"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000292e"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm015507e"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.7b00537"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14020203"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12020165"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13091349"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-022-03881-3"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.30"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70336","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70336","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:08:32Z","timestamp":1792001312000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,4]]},"references-count":46,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,14]]}},"alternative-id":["10.1002\/cmdc.70336"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70336","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,4]]},"assertion":[{"value":"2025-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70336"}}