{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:01:17Z","timestamp":1784869277411,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations \u2264 5 \u03bcM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies.<\/jats:p>","DOI":"10.3390\/cells15141314","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"1314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotype-Oriented Characterization of NSC828786 Identifies Convergent HPN-AMACR-Associated Transcriptomic Signatures in Prostate Adenocarcinoma and Broad-Spectrum Antiproliferative Activity"],"prefix":"10.3390","volume":"15","author":[{"given":"Ya-Ting","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Wan Fang Hospital, Taipei Medical University, Taipei 11681, Taiwan"},{"name":"Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-540X","authenticated-orcid":false,"given":"Rosario Trijuliamos","family":"Manalu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Faculty of Pharmacy, National Institute of Science and Technology, Jakarta 12630, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Lin","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Cheng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruey-Shyang","family":"Soong","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-8946","authenticated-orcid":false,"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Internal Medicine, National Defense Medical University, Taipei 11402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam Rachmawati","family":"Sumitra","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Liang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-6410","authenticated-orcid":false,"given":"Shih-Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-2992","authenticated-orcid":false,"given":"Sung-Ling","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chuan","family":"Yen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-896X","authenticated-orcid":false,"given":"Hong-Jaan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0676-5875","authenticated-orcid":false,"given":"Bashir","family":"Lawal","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0178-6530","authenticated-orcid":false,"given":"Alexander T. H.","family":"Wu","sequence":"additional","affiliation":[{"name":"The Ph.D. Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Taipei Heart Institute (THI), Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-5182","authenticated-orcid":false,"given":"Hsu-Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"School of Pharmacy, National Defense Medical University, Taipei 11490, Taiwan"},{"name":"Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41698-026-01368-3","article-title":"Genomic landscape and precision therapy in prostate cancer: Current status and future directions","volume":"10","author":"Ligon","year":"2026","journal-title":"npj Precis. 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