{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:07:46Z","timestamp":1789135666047,"version":"build-2803163510"},"reference-count":25,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010676","name":"H2020 Societal Challenges","doi-asserted-by":"publisher","award":["848077"],"award-info":[{"award-number":["848077"]}],"id":[{"id":"10.13039\/100010676","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016308","name":"Bpifrance","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100016308","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018703","name":"HORIZON EUROPE European Innovation Council","doi-asserted-by":"publisher","award":["190138295"],"award-info":[{"award-number":["190138295"]}],"id":[{"id":"10.13039\/100018703","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO325"],"award-info":[{"award-number":["KFO325"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LA2829\/15-1"],"award-info":[{"award-number":["LA2829\/15-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Members of the DYRK kinase family have been implicated in the regulation of key metabolic processes. In particular, DYRK1B plays a central role in hepatic lipid metabolism and fatty liver disease. Notably, these functions depend not only on the enzyme\u2019s catalytic activity but also on scaffolding properties. Consequently, therapeutic ambitions aiming to target the entire spectrum of DYRK1B functions must inactivate or eliminate the protein itself rather than merely inhibiting its enzymatic activity, as is achieved by current kinase inhibitors. In this study, we describe a small molecule from the leucettinib class of DYRK inhibitors (LCTB-92) that not only suppresses DYRK kinase activity but also promotes selective ablation of the DYRK1B protein while sparing the closely related paralog DYRK1A. The identification of this compound establishes a foundation for the development of selective agents capable of targeting the entire DYRK1B protein scaffold, thereby addressing catalytic-dependent as well as catalytic-independent kinase functions.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00238","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:00:20Z","timestamp":1788354020000},"page":"2419-2425","source":"Crossref","is-referenced-by-count":0,"title":["Small-Molecule-Mediated\nDepletion of the Dual-Specificity\nTyrosine Phosphorylation-Regulated Kinase 1B (DYRK1B) Protein Scaffold"],"prefix":"10.1021","volume":"9","author":[{"given":"Miriam","family":"Ems","sequence":"first","affiliation":[{"name":"Philipps University Marburg , , ,","place":["Marburg, Germany, 35043"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-8163","authenticated-orcid":true,"given":"Mattias F.","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Perha Pharmaceuticals , , , ,","place":["Roscoff, Bretagne, France, 29680"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Adhikary","sequence":"additional","affiliation":[{"name":"Philipps University Marburg , , ,","place":["Marburg, Germany, 35043"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-4916","authenticated-orcid":true,"given":"Laurent","family":"Meijer","sequence":"additional","affiliation":[{"name":"Perha Pharmaceuticals , , , ,","place":["Roscoff, Bretagne, France, 29680"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-5384","authenticated-orcid":true,"given":"Matthias","family":"Lauth","sequence":"additional","affiliation":[{"name":"Philipps University Marburg , , ,","place":["Marburg, Germany, 35043"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"2026091109133394000_cit1","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1136\/gutjnl-2023-331854","article-title":"DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic\ncancer","volume":"73","author":"Brichkina","year":"2024","journal-title":"Gut"},{"key":"2026091109133394000_cit2","doi-asserted-by":"publisher","first-page":"833","DOI":"10.18632\/oncotarget.13662","article-title":"DYRK1B blocks canonical and promotes\nnon-canonical Hedgehog signaling through activation of the mTOR\/AKT\npathway","volume":"8","author":"Singh","year":"2017","journal-title":"Oncotarget"},{"key":"2026091109133394000_cit3","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.3389\/fimmu.2018.01425","article-title":"Chromatin Binding of\nc-REL and p65 Is Not Limiting for Macrophage\nIL12B Transcription During Immediate Suppression by Ovarian Carcinoma\nAscites","volume":"9","author":"Unger","year":"2018","journal-title":"Front. Immunol."},{"key":"2026091109133394000_cit4","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.3390\/cancers12082106","article-title":"The DYRK Family\nof Kinases in Cancer: Molecular Functions and Therapeutic Opportunities","volume":"12","author":"Boni","year":"2020","journal-title":"Cancers"},{"key":"2026091109133394000_cit5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/jdb5040013","article-title":"Emerging Roles of DYRK\nKinases in Embryogenesis and Hedgehog Pathway\nControl","volume":"5","author":"Singh","year":"2017","journal-title":"J. Dev. Biol."},{"key":"2026091109133394000_cit6","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.3390\/ijms22116047","article-title":"Dual-Specificity, Tyrosine Phosphorylation-Regulated\nKinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an\nOverview","volume":"22","author":"Lindberg","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2026091109133394000_cit7","doi-asserted-by":"publisher","first-page":"R488","DOI":"10.1016\/j.cub.2015.02.067","article-title":"DYRK protein kinases","volume":"25","author":"Soppa","year":"2015","journal-title":"Curr. Biol."},{"key":"2026091109133394000_cit8","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1136\/gutjnl-2018-316128","article-title":"DYRK1A modulates c-MET\nin pancreatic ductal adenocarcinoma to drive\ntumour growth","volume":"68","author":"Luna","year":"2019","journal-title":"Gut"},{"key":"2026091109133394000_cit9","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1056\/NEJMoa1301824","article-title":"A form of the metabolic\nsyndrome associated with mutations in DYRK1B","volume":"370","author":"Keramati","year":"2014","journal-title":"N. Engl. J. 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Rep."},{"key":"2026091109133394000_cit13","doi-asserted-by":"publisher","first-page":"e153724","DOI":"10.1172\/JCI153724","article-title":"Dyrk1b promotes\nhepatic lipogenesis by bypassing canonical insulin signaling and directly\nactivating mTORC2 in mice","volume":"132","author":"Bhat","year":"2022","journal-title":"J. Clin. 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