{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T05:48:31Z","timestamp":1776491311572,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prostate cancer is the most common form of male cancer and can initially be treated as a localized disease. Although the 5\u2010year survival rate at diagnosis approaches 100 percent, a subset of patients will subsequently develop resistance to treatment. This may ultimately lead to metastatic castration resistant prostate cancer (mCRPC), for which the prognosis is much less favorable. The importance of the Wnt\/\u03b2\u2010catenin pathway in treatment\u2010resistant prostate cancer has inspired efforts to exploit the interaction of \u03b2\u2010catenin with its transcription binding partners as a therapeutic strategy for prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peptoid\u2010peptide macrocycles are attractive design scaffolds for disrupting protein\u2010protein interactions. In this study, we evaluate a library of these macrocycles and demonstrate their selectivity for the \u03b2\u2010catenin\/TCF (<jats:bold><jats:styled-content>T C<\/jats:styled-content><\/jats:bold>ell <jats:bold><jats:styled-content>F<\/jats:styled-content><\/jats:bold>actor) interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Importantly, we show that the macrocycles do not significantly alter the binding of \u03b2\u2010catenin to cell surface protein, E\u2010cadherin. Our lead sequence, <jats:bold>Macrocycle 13, (MC13)<\/jats:bold> was also tolerant of modifications aimed to improve aqueous solubility while retaining activity. Herein, we demonstrate in vivo proof of principle for using peptidomimetic macrocycles to target the \u03b2\u2010catenin\/TCF interaction. Treated prostate cancer mouse xenografts show markedly diminished tumor growth and decreased levels of myc protein. <jats:bold>MC13<\/jats:bold> also inhibits growth in an organoid model with genetic alterations frequently found in prostate cancer. Transcriptome analysis of prostate cancer cells treated with <jats:bold>MC13<\/jats:bold> reveals downregulation of key pathways, including Wnt\/\u03b2\u2010catenin and c\u2010myc. Furthermore, chromatin immunoprecipitation (ChIP) analysis shows reduced \u03b2\u2010catenin at its target genes, axin2 and c\u2010myc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings underscore the therapeutic potential of peptoid\u2010peptide macrocycle inhibition of \u03b2\u2010catenin in prostate cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24868","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:30:38Z","timestamp":1739763038000},"page":"646-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vivo Efficacy of a Macrocyclic Peptoid\u2010Peptide Hybrid That Selectively Modulates the Beta\u2010Catenin\/TCF Interaction to Inhibit Prostate Cancer"],"prefix":"10.1002","volume":"85","author":[{"given":"Justine","family":"Habault","sequence":"first","affiliation":[{"name":"Department of Microbiology NYU Grossman School of Medicine New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Franco","sequence":"additional","affiliation":[{"name":"Chemistry Department New York University New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Urology NYU Grossman School of Medicine New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffry A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Urology NYU Grossman School of Medicine New York New York USA"},{"name":"Department of Biochemistry and Molecular Pharmacology NYU Grossman School of Medicine New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maud","family":"Voisin","sequence":"additional","affiliation":[{"name":"Department of Microbiology NYU Grossman School of Medicine New York New 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