{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T01:54:21Z","timestamp":1794275661007,"version":"4.9.0"},"reference-count":75,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004605","name":"Zhengzhou University","doi-asserted-by":"publisher","award":["K2022-010"],"award-info":[{"award-number":["K2022-010"]}],"id":[{"id":"10.13039\/501100004605","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874284"],"award-info":[{"award-number":["81874284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22037003"],"award-info":[{"award-number":["22037003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81820108029"],"award-info":[{"award-number":["81820108029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8182010804"],"award-info":[{"award-number":["8182010804"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973158"],"award-info":[{"award-number":["81973158"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["SQ2019YFE0197900"],"award-info":[{"award-number":["SQ2019YFE0197900"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515011020"],"award-info":[{"award-number":["2022A1515011020"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2018B030337001"],"award-info":[{"award-number":["2018B030337001"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004024","name":"Jinan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008865","name":"Xiamen University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008865","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":[[2022,12]]},"DOI":"10.1016\/j.ejmech.2022.114862","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T11:50:27Z","timestamp":1666353027000},"page":"114862","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["1-Methyl-3-((4-(quinolin-4-yloxy)phenyl)amino)-1H-pyrazole-4-carboxamide derivatives as new rearranged during Transfection (RET) kinase inhibitors capable of suppressing resistant mutants in solvent-front regions"],"prefix":"10.1016","volume":"244","author":[{"given":"Yunong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinpan","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Chao","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengtao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-812X","authenticated-orcid":false,"given":"Ke","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2022.114862_bib1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/0092-8674(85)90115-1","article-title":"Activation of a novel human transforming gene, RET, by DNA rearrangement","volume":"42","author":"Takahashi","year":"1985","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2022.114862_bib2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.cellsig.2004.10.012","article-title":"Direct interactions among Ret, GDNF and GFR\u03b11 molecules reveal new insights into the assembly of a functional three-protein complex","volume":"17","author":"Amoresano","year":"2005","journal-title":"Cell. Signal."},{"key":"10.1016\/j.ejmech.2022.114862_bib3","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1016\/j.bbapap.2012.10.008","article-title":"Structural studies of GDNF family ligands with their receptors\u2014insights into ligand recognition and activation of receptor tyrosine kinase RET","volume":"1834","author":"Wang","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2022.114862_bib4","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.3390\/ijms21197108","article-title":"RET receptor tyrosine kinase: role in neurodegeneration, obesity, and cancer","volume":"21","author":"Mahato","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2022.114862_bib5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.cytogfr.2005.05.010","article-title":"RET tyrosine kinase signaling in development and cancer","volume":"16","author":"Arighi","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.ejmech.2022.114862_bib6","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1158\/2159-8290.CD-19-1116","article-title":"Advances in targeting RET-dependent cancers","volume":"10","author":"Subbiah","year":"2020","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2022.114862_bib7","doi-asserted-by":"crossref","first-page":"924","DOI":"10.3389\/fgene.2019.00924","article-title":"Functional studies on novel RET mutations and their implications for genetic counseling for hirschsprung disease","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Genet."},{"key":"10.1016\/j.ejmech.2022.114862_bib8","doi-asserted-by":"crossref","first-page":"T29","DOI":"10.1530\/ERC-17-0209","article-title":"A comprehensive review on MEN2B","volume":"25","author":"Castinetti","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"10.1016\/j.ejmech.2022.114862_bib9","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1210\/jc.2014-4153","article-title":"RET fusion as a novel driver of medullary thyroid carcinoma","volume":"100","author":"Grubbs","year":"2015","journal-title":"J. Clin. Endocrinal. Metab."},{"key":"10.1016\/j.ejmech.2022.114862_bib10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrendo.2016.11","article-title":"A comprehensive overview of the role of the RET proto-oncogene in thyroid Carcinoma","volume":"12","author":"Romei","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.ejmech.2022.114862_bib11","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1038\/ncomms5846","article-title":"The landscape of kinase fusions in cancer","volume":"5","author":"Stransky","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2022.114862_bib12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrclinonc.2017.175","article-title":"Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes","volume":"15","author":"Drilon","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/path.5005","article-title":"Genetic landscape of papillary thyroid carcinoma in the Chinese population","volume":"244","author":"Liang","year":"2018","journal-title":"J. Pathol."},{"key":"10.1016\/j.ejmech.2022.114862_bib14","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/j.1365-2559.2010.03646.x","article-title":"RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components","volume":"57","author":"Mochizuki","year":"2010","journal-title":"Histopathology"},{"key":"10.1016\/j.ejmech.2022.114862_bib15","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1158\/1078-0432.CCR-16-1679","article-title":"RET aberrations in diverse cancers: next-generation sequencing of 4,871 Patients","volume":"23","author":"Kato","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2022.114862_bib16","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.trecan.2021.07.003","article-title":"Precision therapy for RET-altered cancers with RET inhibitors","volume":"7","author":"Thein","year":"2021","journal-title":"Trends Cancer"},{"key":"10.1016\/j.ejmech.2022.114862_bib17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jtho.2017.10.021","article-title":"Clinical and translational implications of RET rearrangements in non-small cell lung cancer","volume":"13","author":"Ferrara","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib18","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1200\/JCO.2016.70.9352","article-title":"Targeting RET in patients with RET-rearranged lung cancers: results from the global, multicenter RET registry","volume":"35","author":"Gautschi","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib19","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1200\/JCO.19.02551","article-title":"State-of-the-art strategies for targeting RET-dependent cancers","volume":"38","author":"Subbiah","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib20","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrendo.2016.11","article-title":"A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma","volume":"12","author":"Romei","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.ejmech.2022.114862_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2021.102153","article-title":"Diagnostics, therapeutics and RET inhibitor resistance for RET fusion-positive non-small cell lung cancers and future perspectives","volume":"96","author":"Lu","year":"2021","journal-title":"Cancer Treat Rev."},{"key":"10.1016\/j.ejmech.2022.114862_bib22","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/S1470-2045(16)30562-9","article-title":"Cabozantinib in Patients with Advanced RET-rearranged non-small-cell lung cancer: an open-Label, single-centre, phase 2, single-arm trial","volume":"17","author":"Drilon","year":"2016","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib23","first-page":"292","volume":"28","author":"Lee","year":"2017","journal-title":"Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial"},{"key":"10.1016\/j.ejmech.2022.114862_bib24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.lungcan.2019.09.011","article-title":"A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma","volume":"138","author":"Hida","year":"2019","journal-title":"Lung Cancer"},{"key":"10.1016\/j.ejmech.2022.114862_bib25","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1200\/JCO.2008.16.3279","article-title":"Phase II trial of sorafenib in advanced thyroid cancer","volume":"26","author":"Gupta-Abramson","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1200\/JCO.2011.35.5040","article-title":"Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial","volume":"30","author":"Wells","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib27","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1200\/JCO.2012.48.4659","article-title":"Cabozantinib in progressive medullary thyroid cancer","volume":"31","author":"Elisei","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(14)60421-9","article-title":"Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial","volume":"384","author":"Brose","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.ejmech.2022.114862_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2022.102372","article-title":"Resistance to RET targeted therapy in thyroid cancer: molecular basis and overcoming strategies","volume":"105","author":"Rom\u00e1n-Gil","year":"2022","journal-title":"Cancer Treat Rev."},{"key":"10.1016\/j.ejmech.2022.114862_bib30","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.1111\/bph.14395","article-title":"Drug resistance profiles of mutations in the RET kinase domain","volume":"175","author":"Liu","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114862_bib31","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41467-018-02994-7","article-title":"A secondary RET mutation in the activation loop conferring resistance to vandetanib","volume":"9","author":"Nakaoku","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2022.114862_bib32","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1093\/annonc\/mdy137","article-title":"Selective RET kinase inhibition for patients with RET-altered cancers","volume":"29","author":"Subbiah","year":"2018","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib33","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1158\/2159-8290.CD-18-0338","article-title":"Precision targeted therapy with BLU-667 for RET-driven cancers","volume":"8","author":"Subbiah","year":"2018","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2022.114862_bib34","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1200\/JCO.2021.39.15_suppl.3008","article-title":"BOS172738, a highly potent and selective RET inhibitor, for the treatment of RET-altered tumors including RET-fusion+ NSCLC and RET-mutant MTC: phase 1 study results","volume":"39","author":"Schoffski","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib35","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1200\/JCO.2019.37.15_suppl.TPS3162","article-title":"A phase I study of BOS172738 in patients with advanced solid tumors with RET gene alterations including non-small cell lung cancer and medullary thyroid cancer","volume":"37","author":"Schoffski","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1021\/acsmedchemlett.8b00035","article-title":"Discovery of a first-in-class gut-restricted RET kinase inhibitor as a clinical candidate for the treatment of IBS","volume":"9","author":"Eidam","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib37","doi-asserted-by":"crossref","first-page":"7777","DOI":"10.1021\/jm8007823","article-title":"Synthesis, modeling, and RET protein kinase inhibitory activity of 3- and 4-substituted \u03b2-carbolin-1-ones","volume":"51","author":"Cincinelli","year":"2008","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib38","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1021\/acsmedchemlett.1c00450","article-title":"Antitarget selectivity and tolerability of novel pyrrolo[2,3-d]pyrimidine RET inhibitors","volume":"12","author":"Mathison","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib39","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1021\/acsmedchemlett.9b00615","article-title":"Discovery and optimization of wt-RET\/KDR-selective inhibitors of RETV804M Kinase","volume":"11","author":"Newton","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib40","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1158\/2159-8290.CD-18-0839","article-title":"A phase I\/Ib trial of the VEGFR-sparing multikinase RET inhibitor RXDX-105","volume":"9","author":"Drilon","year":"2019","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2022.114862_bib41","doi-asserted-by":"crossref","first-page":"8717","DOI":"10.1002\/anie.201501104","article-title":"Fragment-based discovery of a dual pan-RET\/VEGFR2 kinase inhibitor optimized for single-agent polypharmacology","volume":"54","author":"Frett","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2022.114862_bib42","doi-asserted-by":"crossref","first-page":"4506","DOI":"10.1021\/acs.jmedchem.9b01336","article-title":"Bioisosteric discovery of NPA101.3, a second-generation RET\/VEGFR2 Inhibitor optimized for single-agent polypharmacology","volume":"63","author":"Moccia","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib43","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1021\/acsmedchemlett.0c00015","article-title":"Efficacy and tolerability of pyrazolo[1,5-a]pyrimidine RET kinase inhibitors for the treatment of lung adenocarcinoma","volume":"11","author":"Mathison","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib44","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1021\/acs.jmedchem.5b01522","article-title":"A pyrazolo[3,4-d]pyrimidin-4-amine derivative containing an isoxazole moiety is a selective and potent inhibitor of RET gatekeeper mutants","volume":"59","author":"Yoon","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2021.128149","article-title":"Discovery and optimization of selective RET inhibitors via scaffold hopping","volume":"47","author":"Luo","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112691","article-title":"Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: design, synthesis and biological evaluation","volume":"206","author":"Lakkaniga","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib47","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1021\/acschembio.9b00407","article-title":"Leveraging atropisomerism to obtain a selective inhibitor of RET kinase with secondary activities toward EGFR mutants","volume":"14","author":"Toenjes","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2022.114862_bib48","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1021\/jm3003944","article-title":"Preparation of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET kinase inhibitors","volume":"55","author":"Din\u00e9r","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0128364","article-title":"Identification of novel small molecule inhibitors of oncogenic RET kinase","volume":"10","author":"Moccia","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2022.114862_bib50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1021\/ml500402t","article-title":"RET kinase inhibitors may treat cancer and gastrointestinal disorders","volume":"6","author":"Abdel-Magid","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.114862_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114226","article-title":"Design and development of photoswitchable DFG-Out RET kinase inhibitors","volume":"234","author":"Xu","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib52","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112755","article-title":"Discovery of 4-methyl-N-(4-((4-methylpiperazin- 1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((6-(pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-oxy)benzamide as a potent inhibitor of RET and its gatekeeper mutant","volume":"207","author":"Li","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib53","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ejmech.2018.02.080","article-title":"Challenging clinically unresponsive medullary thyroid cancer: discovery and pharmacological activity of novel RET inhibitors","volume":"150","author":"Pietra","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib54","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ejmech.2016.01.039","article-title":"The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity","volume":"112","author":"Newton","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib55","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.ejmech.2014.09.023","article-title":"Identification of two novel RET kinase inhibitors through MCR-based drug discovery: design, synthesis and evaluation","volume":"86","author":"Frett","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib56","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ejmech.2016.10.050","article-title":"Identification of a novel 5-amino-3-(5-cyclopropylisoxazol-3-yl)-1-isopropyl-1H-pyrazole-4-carboxamide as a specific RET kinase inhibitor","volume":"125","author":"Yoon","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib57","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.ejmech.2017.09.018","article-title":"Structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of inhibitors of RET and its drug resistance mutants","volume":"143","author":"Yang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib58","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jtho.2020.01.006","article-title":"RET solvent front mutations mediate acquired resistance to selective RET inhibition in RET-driven malignancies","volume":"15","author":"Solomon","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib59","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.annonc.2020.10.599","article-title":"Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations","volume":"32","author":"Subbiah","year":"2021","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib60","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1021\/acs.jmedchem.1c01280","article-title":"Discovery of N-trisubstituted pyrimidine derivatives as Type I RET and RET gatekeeper mutant inhibitors with a novel kinase binding pose","volume":"65","author":"Zhang","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib61","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-95612-4","article-title":"Targeted activity of the small molecule kinase inhibitor Pz-1 towards RET and TRK kinases","volume":"11","author":"Moccia","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2022.114862_bib62","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/annonc\/mdz244.068","article-title":"TPX-0046 is a novel and potent RET\/SRC inhibitor for RET-driven cancers","volume":"30","author":"Drilon","year":"2019","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib63","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3390\/cancers13051091","article-title":"Chasing the target: new phenomena of resistance to novel selective RET inhibitors in lung cancer. Updated evidence and future perspectives","volume":"13","author":"Fancelli","year":"2021","journal-title":"Cancers"},{"key":"10.1016\/j.ejmech.2022.114862_bib64","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1158\/1538-7445.AM2021-1464","article-title":"Abstract 1464: pre-clinical characterization of potent and selective next-generation RET inhibitors","volume":"81","author":"Kolakowski","year":"2021","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2022.114862_bib65","series-title":"Condensed Pyrimidine Compound or Salt Thereof, Applicant","author":"Miyazaki","year":"2017"},{"key":"10.1016\/j.ejmech.2022.114862_bib66","doi-asserted-by":"crossref","first-page":"e15107","DOI":"10.1200\/JCO.2022.40.16_suppl.e15107","article-title":"The development of APS03118, a potent next-generation RET inhibitor for treating RET-inhibitor-resistant patients","volume":"40","author":"Subbiah","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib67","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tips.2021.04.001","article-title":"Fragment-based drug design facilitates selective kinase inhibitor discovery","volume":"42","author":"Wang","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2022.114862_bib68","series-title":"Substituted Pyrazolopyrimidines","author":"Bacon","year":"2007"},{"key":"10.1016\/j.ejmech.2022.114862_bib69","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1021\/acs.jmedchem.7b00010","article-title":"Synthetic approaches to the new drugs approved during 2015","volume":"60","author":"Flick","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114862_bib70","series-title":"Compounds for the Treatment of Kinase-dependent Disorders","author":"Bannen","year":"2021"},{"key":"10.1016\/j.ejmech.2022.114862_bib71","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/CCO.0b013e328011a25f","article-title":"Ba\/F3 cells and their use in kinase drug discovery","volume":"19","author":"Warmuth","year":"2007","journal-title":"Curr. Opin. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib72","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/JTO.0000000000000337","article-title":"A mass spectrometry assay to simultaneously analyze ROS1 and RET fusion gene expression in non-small-cell lung cancer","volume":"10","author":"Wijesinghe","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"10.1016\/j.ejmech.2022.114862_bib73","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1093\/carcin\/bgu158","article-title":"A mouse model of KIF5B-RET fusion-dependent lung tumorigenesis","volume":"35","author":"Saito","year":"2014","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.ejmech.2022.114862_bib74","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.2174\/1389201017666160808160513","article-title":"Cell proliferation and cytotoxicity assays","volume":"17","author":"Adan","year":"2016","journal-title":"Curr. Pharmaceut. Biotechnol."},{"key":"10.1016\/j.ejmech.2022.114862_bib75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-61779-108-6_1","article-title":"Cell viability assays: introduction","volume":"740","author":"Stoddart","year":"2011","journal-title":"Methods Mol. Biol."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422007644?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422007644?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:04:24Z","timestamp":1777529064000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523422007644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":75,"alternative-id":["S0223523422007644"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114862","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"1-Methyl-3-((4-(quinolin-4-yloxy)phenyl)amino)-1H-pyrazole-4-carboxamide derivatives as new rearranged during Transfection (RET) kinase inhibitors capable of suppressing resistant mutants in solvent-front regions","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114862","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114862"}}