{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:34:23Z","timestamp":1786988063951,"version":"build-2736575974"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"am","delay-in-days":328,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.ejmech.2021.113158","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T03:46:31Z","timestamp":1610509591000},"page":"113158","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Discovery of 3-phenyl- and 3-N-piperidinyl-isothiazolo[4,3-b]pyridines as highly potent inhibitors of cyclin G-associated kinase"],"prefix":"10.1016","volume":"213","author":[{"given":"Bel\u00e9n","family":"Martinez-Gualda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-9418","authenticated-orcid":false,"given":"Sirle","family":"Saul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-6540","authenticated-orcid":false,"given":"Mathy","family":"Froeyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-5850","authenticated-orcid":false,"given":"Dominique","family":"Schols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet","family":"Herdewijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirit","family":"Einav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3872-6558","authenticated-orcid":false,"given":"Steven","family":"De Jonghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2021.113158_bib1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.str.2015.12.015","article-title":"Family-wide structural analysis of human Numb-associated protein kinases","volume":"24","author":"Sorrell","year":"2016","journal-title":"Structure"},{"issue":"8","key":"10.1016\/j.ejmech.2021.113158_bib2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm3151","article-title":"Molecular mechanism and physiological functions of clathrin-mediated endocytosis","volume":"12","author":"McMahon","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejmech.2021.113158_bib3","doi-asserted-by":"crossref","first-page":"9521","DOI":"10.1083\/jcb.200111068","article-title":"Phosphorylation of the AP2 \u03bc-subunit by AAK1 mediates high affinity binding to membrane protein sorting signals","volume":"156","author":"Ricotta","year":"2002","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.ejmech.2021.113158_bib4","doi-asserted-by":"crossref","first-page":"10296","DOI":"10.1073\/pnas.0403175101","article-title":"The serine\/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling","volume":"101","author":"Zhang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"issue":"5","key":"10.1016\/j.ejmech.2021.113158_bib5","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nrm.2017.132","article-title":"Mechanisms of clathrin-mediated endocytosis","volume":"19","author":"Kaksonen","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"5","key":"10.1016\/j.ejmech.2021.113158_bib6","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1083\/jcb.200211080","article-title":"AP-1 binding to sorting signals and release from clathrin-coated vesicles is regulated by phosphorylation","volume":"160","author":"Ghosh","year":"2003","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.ejmech.2021.113158_bib7","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1242\/jcs.113.12.2093","article-title":"Bi-directional trafficking between the trans-Golgi network and the endosomal\/lysosomal system","volume":"113","author":"Rohn","year":"2000","journal-title":"J.\u00a0Cell Sci."},{"issue":"12","key":"10.1016\/j.ejmech.2021.113158_bib8","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/j.1600-0854.2005.00346.x","article-title":"Multiple roles for cyclin G-associated kinase in clathrin-mediated sorting events","volume":"6","author":"Zhang","year":"2005","journal-title":"Traffic"},{"key":"10.1016\/j.ejmech.2021.113158_bib9","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1073\/pnas.1318306111","article-title":"Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease","volume":"111","author":"Beilina","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2021.113158_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0100124","article-title":"Gefitinib and luteolin cause growth arrest of human prostate cancer PC-3 cells via inhibition of cyclin G-associated kinase and induction of miR-630","volume":"9","author":"Sakurai","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2021.113158_bib11","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1158\/1535-7163.MCT-10-0637","article-title":"Cyclin G\u2013associated kinase is necessary for osteosarcoma cell proliferation and receptor trafficking","volume":"12","author":"Susa","year":"2010","journal-title":"Mol. Canc. Ther."},{"issue":"8","key":"10.1016\/j.ejmech.2021.113158_bib12","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1128\/JVI.02705-14","article-title":"AP-2-sssociated protein kinase 1 and cyclin G-associated kinase regulate Hepatitis C virus entry and are potential drug targets","volume":"89","author":"Neveu","year":"2015","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2021.113158_bib13","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1126\/science.aaa3778","article-title":"Infectious disease. Combating emerging viral threats","volume":"348","author":"Bekerman","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2021.113158_bib14","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.cell.2015.07.005","article-title":"Molecular insight into dengue virus pathogenesis and its implications for disease control","volume":"162","author":"Diamond","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2021.113158_bib15","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.12688\/f1000research.19197.1","article-title":"Recent advances in understanding dengue","volume":"8","author":"Halstead","year":"2019","journal-title":"F1000Research (F1000 Faculty Rev"},{"issue":"8","key":"10.1016\/j.ejmech.2021.113158_bib17","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1586\/14760584.2013.815412","article-title":"Dengue vaccines: recent developments, ongoing challenges and current candidates","volume":"12","author":"McArthur","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"10.1016\/j.ejmech.2021.113158_bib18","doi-asserted-by":"crossref","first-page":"5622","DOI":"10.1021\/acs.jmedchem.5b01653","article-title":"The medicinal chemistry of dengue virus","volume":"59","author":"Behnam","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib19","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1172\/JCI89857","article-title":"Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects","volume":"127","author":"Bekerman","year":"2017","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ejmech.2021.113158_bib20","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.antiviral.2018.05.001","article-title":"Feasibility and biological rationale of repurposing sunitinib and erlotinib for dengue treatment","volume":"155","author":"Pu","year":"2018","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2021.113158_bib21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nbt1068","article-title":"A\u00a0small molecule\u2013kinase interaction map for clinical kinase inhibitors","volume":"23","author":"Fabian","year":"2005","journal-title":"Nat. Biotechnol."},{"issue":"9","key":"10.1016\/j.ejmech.2021.113158_bib22","doi-asserted-by":"crossref","first-page":"4772","DOI":"10.1021\/acs.jmedchem.9b00350","article-title":"Design of a cyclin G associated kinase (GAK)\/epidermal growth factor receptor (EGFR) inhibitor set to interrogate the relationship of EGFR and GAK in chordoma","volume":"62","author":"Asquith","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2021.113158_bib23","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nbt.1990","article-title":"Comprehensive analysis of kinase inhibitor selectivity","volume":"29","author":"I Davis","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ejmech.2021.113158_bib24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/cmdc.201700663","article-title":"Identification and optimization of 4-anilinoquinolines as inhibitors of cyclin G associated kinase","volume":"13","author":"Asquith","year":"2018","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2021.113158_bib25","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1021\/acs.jmedchem.8b01213","article-title":"SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)","volume":"62","author":"Asquith","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib26","doi-asserted-by":"crossref","first-page":"4016","DOI":"10.3390\/molecules24224016","article-title":"Towards the development of an in\u00a0vivo chemical probe for cyclin G associated kinase (GAK)","volume":"24","author":"Asquith","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2021.113158_bib27","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chembiol.2017.10.010","article-title":"Quantitative, wide-spectrum kinase profiling in LiveCells for assessing the effect of cellular ATP on target engagement","volume":"25","author":"Vasta","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.ejmech.2021.113158_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2020.127284","article-title":"Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines","volume":"30","author":"Saul","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2021.113158_bib29","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1021\/jm501759m","article-title":"Selective inhibitors of cyclin G associated kinase (GAK) as anti-hepatitis C agents","volume":"58","author":"Kovackova","year":"2015","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib30","doi-asserted-by":"crossref","first-page":"6178","DOI":"10.1021\/acs.jmedchem.8b00613","article-title":"Optimisation of isothiazolo[4,3-b]pyridine-based inhibitors of cyclin G associated kinase (GAK) with broad-spectrum antiviral activity","volume":"61","author":"Pu","year":"2018","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib31","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ejmech.2018.11.065","article-title":"Cyclin G-associated kinase (GAK) affinity and antiviral activity studies of a series of 3-C-substituted isothiazolo[4,3-b]pyridines","volume":"163","author":"Wouters","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2019.115188","article-title":"Structure-activity relationship study of the pyridine moiety of isothiazolo[4,3-b]pyridines as antiviral agents targeting cyclin G-associated kinase","volume":"28","author":"Martinez-Gualda","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib33","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1021\/cr00039a007","article-title":"Palladium-catalyzed cross-coupling reactions of organoborn compounds","volume":"95","author":"Miyaura","year":"1995","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2021.113158_bib34","doi-asserted-by":"crossref","first-page":"7528","DOI":"10.3390\/molecules20057528","article-title":"Recent developments in the Suzuki-Miyaura reaction: 2010\u20132014","volume":"20","author":"Maluenda","year":"2015","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2021.113158_bib35","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1002\/ejoc.202000080","article-title":"Amide bond formation strategies: latest advances on a dateless transformation","author":"Massolo","year":"2020","journal-title":"Eur. J. Org. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib36","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1034\/j.1399-3011.2001.00935.x","article-title":"Fast, efficient and selective deprotection of the tert-butoxycarbonyl (Boc) group using HCl\/dioxane (4 M)","volume":"58","author":"Han","year":"2001","journal-title":"J.\u00a0Peptide Res."},{"key":"10.1016\/j.ejmech.2021.113158_bib37","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1177\/1087057109339207","article-title":"Development and applications of a broad-coverage, TR-FRET-based kinase binding assay platform","volume":"14","author":"Lebakken","year":"2009","journal-title":"J.\u00a0Biomol. Screening"},{"key":"10.1016\/j.ejmech.2021.113158_bib38","doi-asserted-by":"crossref","first-page":"275","DOI":"10.7164\/antibiotics.30.275","article-title":"A\u00a0New Alkaloid AM-2282 of Streptomyces Origin. Taxonomy, Fermentation, Isolation and Preliminary Characterization","volume":"vol. 30","author":"Omura","year":"1977","journal-title":"J.\u00a0Antibiot."},{"key":"10.1016\/j.ejmech.2021.113158_bib39","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1432-1033.1995.317_c.x","article-title":"Different susceptibility of protein kinases to Staurosporine inhibition. Kinetic studies and molecular bases for the resistance of protein kinase CK2","volume":"234","author":"Meggio","year":"1995","journal-title":"Eur. J. Biochem"},{"key":"10.1016\/j.ejmech.2021.113158_bib40","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.drudis.2009.07.014","article-title":"The impact of aromatic ring count on compound developability \u2013 are too many aromatic rings a liability in drug design?","volume":"14","author":"Ritchie","year":"2009","journal-title":"Drug Discov. Today"},{"issue":"7","key":"10.1016\/j.ejmech.2021.113158_bib41","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1021\/acs.jcim.8b00222","article-title":"Determination of a focused mini kinase panel for early identification of selective kinase inhibitors","volume":"58","author":"Bembenek","year":"2018","journal-title":"J.\u00a0Chem. Inf. Model"},{"issue":"14","key":"10.1016\/j.ejmech.2021.113158_bib42","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/j.bmcl.2019.05.025","article-title":"Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK)","volume":"29","author":"Asquith","year":"2019","journal-title":"Bioorg. Med. Chem. Lett"},{"issue":"20","key":"10.1016\/j.ejmech.2021.113158_bib43","doi-asserted-by":"crossref","first-page":"5861","DOI":"10.1016\/j.bmcl.2009.08.083","article-title":"Small kinase assay panels can provide a measure of selectivity","volume":"19","author":"Brandt","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2021.113158_bib44","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1128\/JVI.02424-12","article-title":"Membrane topology and function of dengue virus NS2A protein","volume":"87","author":"Xie","year":"2013","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2021.113158_bib45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.antiviral.2011.05.001","article-title":"Development and characterization of a stable luciferase dengue virus for high-throughput screening","volume":"91","author":"Zou","year":"2011","journal-title":"Antiviral Res."},{"issue":"41","key":"10.1016\/j.ejmech.2021.113158_bib46","doi-asserted-by":"crossref","first-page":"13649","DOI":"10.1021\/ja0697875","article-title":"ChemDraw Ultra 10.0\"","volume":"128","author":"Mills","year":"2006","journal-title":"J.\u00a0Am. Chem. Soc."},{"issue":"16","key":"10.1016\/j.ejmech.2021.113158_bib47","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.ejmech.2021.113158_bib48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J.\u00a0Comput. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523421000076?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523421000076?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:22:53Z","timestamp":1759328573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523421000076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":47,"alternative-id":["S0223523421000076"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113158","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of 3-phenyl- and 3-N-piperidinyl-isothiazolo[4,3-b]pyridines as highly potent inhibitors of cyclin G-associated kinase","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113158","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113158"}}