{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:54:36Z","timestamp":1789019676023,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014R1A2A1A11053203"],"award-info":[{"award-number":["2014R1A2A1A11053203"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B2006839"],"award-info":[{"award-number":["2017R1A2B2006839"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gain\u2010 or loss\u2010of\u2010function mutations in Janus kinase 3 (JAK3) contribute to the pathogenesis of various haematopoietic malignancies and immune disorders, suggesting that aberrant JAK3 signalling is an attractive therapeutic target to treat these disorders. In this study, we performed structure\u2010based computational database screening using the 3D structure of the JAK3 kinase domain and the National Cancer Institute diversity set and identified tubulosine as a novel JAK3 inhibitor. Tubulosine directly blocked the catalytic activity of JAK3 by selective interacting with the JAK3 kinase domain. Consistently, tubulosine potently inhibited persistently activated and interleukin\u20102\u2010dependent JAK3, and JAK3\u2010mediated downstream targets. Importantly, it did not affect the activity of other JAK family members, particularly prolactin\u2010induced JAK2\/signal transducer and activator of transcription 5 and interferon alpha\u2010induced JAK1\u2010TYK2\/STAT1. Tubulosine specifically decreased survival and proliferation of cancer cells, in which persistently active JAK3 is expressed, by inducing apoptotic and necrotic\/autophagic cell death without affecting other oncogenic signalling. Collectively, tubulosine is a potential small\u2010molecule compound that selectively inhibits JAK3 activity, suggesting that it may serve as a promising therapeutic candidate for treating disorders caused by aberrant activation of JAK3 signalling.<\/jats:p>","DOI":"10.1111\/jcmm.15362","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T19:19:54Z","timestamp":1592421594000},"page":"7427-7438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tubulosine selectively inhibits JAK3 signalling by binding to the ATP\u2010binding site of the kinase of JAK3"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-6616","authenticated-orcid":false,"given":"Byung\u2010Hak","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics New York Medical College Valhalla NY USA"},{"name":"Department of Pharmacology Seoul National University 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