{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:14:42Z","timestamp":1782972882667,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Prostatic cancer (PCa) is a common malignant neoplasm in men worldwide. Most patients develop castration-resistant prostate cancer (CRPC) after treatment with androgen deprivation therapy (ADT), usually resulting in death. Therefore, investigating new therapeutic targets and drugs for PCa patients is urgently needed. Nuclear Dbf2-related kinase 1 (NDR1), also known as STK38, is a serine\/threonine kinase in the NDR\/LATS kinase family that plays a critical role in cellular processes, including immunity, inflammation, metastasis, and tumorigenesis. It was reported that NDR1 inhibited the metastasis of prostate cancer cells by suppressing epithelial-mesenchymal transition (EMT), and decreased NDR1 expression might lead to a poorer prognosis, suggesting the enormous potential of NDR1 in antitumorigenesis. In this study, we characterized a small-molecule agonist named aNDR1, which specifically bound to NDR1 and potently promoted NDR1 expression, enzymatic activity and phosphorylation. aNDR1 exhibited drug-like properties, such as favorable stability, plasma protein binding capacity, cell membrane permeability, and PCa cell-specific inhibition, while having no obvious effect on normal prostate cells. Meanwhile, aNDR1 exhibited good antitumor activity both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. aNDR1 inhibited proliferation and migration of PCa cells and promoted apoptosis of PCa cells <jats:italic>in vitro<\/jats:italic>. We further found that aNDR1 inhibited subcutaneous tumors and lung metastatic nodules <jats:italic>in vivo<\/jats:italic>, with no obvious toxicity to the body. In summary, our study presents a potential small-molecule lead compound that targets NDR1 for clinical therapy of PCa patients.<\/jats:p>","DOI":"10.3389\/fphar.2024.1367358","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T16:58:36Z","timestamp":1707757116000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of a small-molecule NDR1 agonist for prostate cancer therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Yang","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyuan","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuodong","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyuan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1021\/acs.jmedchem.0c01516","article-title":"A decade of FDA-approved drugs (2010-2019): trends and future directions","volume":"64","author":"Brown","year":"2021","journal-title":"J. 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