{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:11:16Z","timestamp":1789510276965,"version":"build-2803163510"},"reference-count":26,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,10]]},"DOI":"10.1016\/j.ejmech.2023.115628","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T02:28:42Z","timestamp":1688696922000},"page":"115628","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Design, synthesis and biological evaluation of indazole derivatives as selective covalent inhibitors of FGFR4 in wild-type and gatekeeper mutants"],"prefix":"10.1016","volume":"258","author":[{"given":"Yingyue","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangsheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9297-6665","authenticated-orcid":false,"given":"Luoting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.ejmech.2023.115628_bib1","first-page":"209","article-title":"Global cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"Ca - Cancer J. Clin."},{"issue":"1","key":"10.1016\/j.ejmech.2023.115628_bib2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"issue":"5","key":"10.1016\/j.ejmech.2023.115628_bib3","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1002\/hep.32740","article-title":"The liver cancer immune microenvironment: therapeutic implications for hepatocellular carcinoma","volume":"77","author":"Donne","year":"2023","journal-title":"Hepatology"},{"issue":"28","key":"10.1016\/j.ejmech.2023.115628_bib4","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1200\/JCO.2012.44.5643","article-title":"Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil\/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia","volume":"31","author":"Qin","year":"2013","journal-title":"J. Clin. Oncol."},{"issue":"3","key":"10.1016\/j.ejmech.2023.115628_bib5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The fibroblast growth factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"issue":"2","key":"10.1016\/j.ejmech.2023.115628_bib6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nrc2780","article-title":"Fibroblast growth factor signalling: from development to cancer","volume":"10","author":"Turner","year":"2010","journal-title":"Nat. Rev. Cancer"},{"issue":"17","key":"10.1016\/j.ejmech.2023.115628_bib7","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.4155\/fmc-2018-0103","article-title":"Recent developments and advances of FGFR as a potential target in cancer","volume":"10","author":"Xue","year":"2018","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115628_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104567","article-title":"The role of fibroblast growth factor receptor (FGFR) protein-tyrosine kinase inhibitors in the treatment of cancers including those of the urinary bladder","volume":"151","author":"Roskoski","year":"2020","journal-title":"Pharmacol. Res."},{"issue":"4","key":"10.1016\/j.ejmech.2023.115628_bib9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10637-016-0416-x","article-title":"Safety, tolerability and pharmacokinetics of the fibroblast growth factor receptor inhibitor AZD4547 in Japanese patients with advanced solid tumours: a Phase I study","volume":"35","author":"Saka","year":"2017","journal-title":"Invest. N. Drugs"},{"issue":"2","key":"10.1016\/j.ejmech.2023.115628_bib10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1200\/JCO.2016.67.2048","volume":"35","author":"Nogova","year":"2017","journal-title":"J. Clin. Oncol."},{"issue":"4","key":"10.1016\/j.ejmech.2023.115628_bib11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3390\/diseases3040294","article-title":"Targeting FGF19\/FGFR4 pathway: a novel therapeutic strategy for hepatocellular carcinoma","volume":"3","author":"Repana","year":"2015","journal-title":"Diseases"},{"issue":"5","key":"10.1016\/j.ejmech.2023.115628_bib12","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0036713","article-title":"Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models","volume":"7","author":"French","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.ejmech.2023.115628_bib13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jhep.2008.08.015","article-title":"Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention","volume":"50","author":"Ho","year":"2009","journal-title":"J. Hepatol."},{"issue":"12","key":"10.1016\/j.ejmech.2023.115628_bib14","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1158\/2159-8290.CD-19-0555","article-title":"First-in-Human phase I study of fisogatinib (BLU-554) validates aberrant FGF19 signaling as a driver event in hepatocellular carcinoma","volume":"9","author":"Kim","year":"2019","journal-title":"Cancer Discov."},{"issue":"24","key":"10.1016\/j.ejmech.2023.115628_bib15","doi-asserted-by":"crossref","first-page":"6999","DOI":"10.1158\/0008-5472.CAN-17-1865","article-title":"H3B-6527 is a potent and selective inhibitor of FGFR4 in FGF19-driven hepatocellular carcinoma","volume":"77","author":"Joshi","year":"2017","journal-title":"Cancer Res."},{"issue":"21","key":"10.1016\/j.ejmech.2023.115628_bib16","doi-asserted-by":"crossref","first-page":"12542","DOI":"10.1021\/acs.jmedchem.0c01019","article-title":"Discovery of roblitinib (FGF401) as a reversible-covalent inhibitor of the kinase activity of fibroblast growth factor receptor 4","volume":"63","author":"Fairhurst","year":"2020","journal-title":"J. Med. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2023.115628_bib17","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1158\/1535-7163.MCT-18-1291","article-title":"FGF401, A first-in-class highly selective and potent FGFR4 inhibitor for the treatment of FGF19-driven hepatocellular cancer","volume":"18","author":"Weiss","year":"2019","journal-title":"Mol. Cancer Therapeut."},{"issue":"12","key":"10.1016\/j.ejmech.2023.115628_bib18","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1158\/2159-8290.CD-19-0367","article-title":"Acquired on-target clinical resistance validates FGFR4 as a driver of hepatocellular carcinoma","volume":"9","author":"Hatlen","year":"2019","journal-title":"Cancer Discov."},{"issue":"24","key":"10.1016\/j.ejmech.2023.115628_bib19","doi-asserted-by":"crossref","first-page":"16570","DOI":"10.1021\/acs.jmedchem.2c01420","article-title":"Discovery of 2-Amino-7-sulfonyl-7H-pyrrolo[2,3-d]pyrimidine derivatives as potent reversible FGFR inhibitors with gatekeeper mutation tolerance: design, synthesis, and biological evaluation","volume":"65","author":"Xie","year":"2022","journal-title":"J. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2023.115628_bib20","first-page":"1604","article-title":"Approaches to selective fibroblast growth factor receptor 4 inhibition through targeting the ATP-pocket middle-hinge region","volume":"8","author":"Fairhurst","year":"2017","journal-title":"J\/OL]"},{"issue":"5","key":"10.1016\/j.ejmech.2023.115628_bib21","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1021\/jm101396q","article-title":"Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors","volume":"54","author":"Leproult","year":"2011","journal-title":"J. Med. Chem."},{"issue":"85","key":"10.1016\/j.ejmech.2023.115628_bib22","doi-asserted-by":"crossref","first-page":"12089","DOI":"10.1039\/C8CC07546H","article-title":"LY2874455 potently inhibits FGFR gatekeeper mutants and overcomes mutation-based resistance","volume":"54","author":"Wu","year":"2018","journal-title":"Chem. Commun."},{"issue":"22","key":"10.1016\/j.ejmech.2023.115628_bib23","doi-asserted-by":"crossref","first-page":"10272","DOI":"10.1021\/acs.jmedchem.9b01169","article-title":"Start selective and rigidify: the discovery path toward a next generation of EGFR tyrosine kinase inhibitors","volume":"62","author":"Engelhardt","year":"2019","journal-title":"J. Med. Chem."},{"issue":"23","key":"10.1016\/j.ejmech.2023.115628_bib24","doi-asserted-by":"crossref","first-page":"14921","DOI":"10.1021\/acs.jmedchem.0c01488","article-title":"N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective janus kinase 2 inhibitors for the treatment of myeloproliferative neoplasms","volume":"63","author":"Yang","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115628_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113219","article-title":"Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer","volume":"214","author":"Chen","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2023.115628_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113794","article-title":"Design, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors","volume":"225","author":"Pan","year":"2021","journal-title":"Eur. J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005949?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523423005949?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:04:13Z","timestamp":1759331053000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523423005949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":26,"alternative-id":["S0223523423005949"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115628","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and biological evaluation of indazole derivatives as selective covalent inhibitors of FGFR4 in wild-type and gatekeeper mutants","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115628","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115628"}}