{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:57:34Z","timestamp":1792785454568,"version":"4.5.0"},"reference-count":24,"publisher":"Informa UK Limited","issue":"1","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1080\/policies-text-data-mining"}],"funder":[{"name":"by the National Research Foundation (NRF) funded by the Korean government","award":["RS-2021-NR061588"],"award-info":[{"award-number":["RS-2021-NR061588"]}]},{"name":"the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government","award":["RS-2024-00344154"],"award-info":[{"award-number":["RS-2024-00344154"]}]},{"name":"the Creative-Pioneering Researchers Program through Seoul National University","id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.tandfonline.com"],"crossmark-restriction":true},"short-container-title":["Journal of Enzyme Inhibition and Medicinal Chemistry"],"published-print":{"date-parts":[[2026,12,31]]},"DOI":"10.1080\/14756366.2026.2730846","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:38:28Z","timestamp":1790350708000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Structure-based rational design and biological evaluation of a quinazoline-based EGFR exon 20 insertion inhibitor"],"prefix":"10.1080","volume":"41","author":[{"given":"Sooheum","family":"Jo","sequence":"first","affiliation":[{"name":"College of Pharmacy, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsoo","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Korea University","place":["Sejong, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Korea University","place":["Sejong, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaebong","family":"Jang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Research Institute of Pharmaceutical Sciences, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Natural Products Research Institute, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"301","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"3","key":"e_1_3_3_2_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.21037\/tlcr.2019.04.12","article-title":"Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment","volume":"8","author":"Zhang T","year":"2019","unstructured":"Zhang T, Wan B, Zhao Y, Li C, Liu H, Lv T, Zhan P, Song Y. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res. 2019;8(3):302\u2013316.","journal-title":"Transl Lung Cancer Res"},{"issue":"2","key":"e_1_3_3_3_1","first-page":"110","article-title":"Epidermal growth factor receptor in non-small cell lung cancer","volume":"4","author":"Prabhakar CN.","year":"2015","unstructured":"Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):110\u2013118.","journal-title":"Transl Lung Cancer Res"},{"issue":"1","key":"e_1_3_3_4_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41392-019-0038-9","article-title":"Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer","volume":"4","author":"Vyse S","year":"2019","unstructured":"Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther. 2019;4(1):5.","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_3_3_5_1","doi-asserted-by":"crossref","first-page":"1399975","DOI":"10.3389\/fimmu.2024.1399975","article-title":"Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations","volume":"15","author":"Hu M","year":"2024","unstructured":"Hu M, Zhong C, Wang J, Chen J, Zhou T. Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations. Front Immunol. 2024;15:1399975.","journal-title":"Front Immunol"},{"issue":"7","key":"e_1_3_3_6_1","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.21037\/tlcr-23-98","article-title":"EGFR exon 20 insertion mutations and ERBB2 mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates","volume":"12","author":"Sentana-Lledo D","year":"2023","unstructured":"Sentana-Lledo D, Academia E, Viray H, Rangachari D, Kobayashi SS, VanderLaan PA, Costa DB. EGFR exon 20 insertion mutations and ERBB2 mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates. Transl Lung Cancer Res. 2023;12(7):1590\u20131610.","journal-title":"Transl Lung Cancer Res"},{"issue":"5","key":"e_1_3_3_7_1","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.3390\/cancers13051120","article-title":"Structural basis for the functional changes by EGFR exon 20 insertion mutations","volume":"13","author":"Tamirat MZ","year":"2021","unstructured":"Tamirat MZ, Kurppa KJ, Elenius K, Johnson MS. Structural basis for the functional changes by EGFR exon 20 insertion mutations. Cancers (Basel). 2021;13(5):1120.","journal-title":"Cancers (Basel)"},{"key":"e_1_3_3_8_1","first-page":"301","article-title":"Tackling drug resistance in EGFR Exon 20 insertion mutant lung cancer","volume":"14","author":"Pacini L","year":"2021","unstructured":"Pacini L, Jenks AD, Vyse S, Wilding CP, Arthur A, Huang PH. Tackling drug resistance in EGFR Exon 20 insertion mutant lung cancer. Pharmgenomics Pers Med. 2021;14:301\u2013317.","journal-title":"Pharmgenomics Pers Med"},{"issue":"11","key":"e_1_3_3_9_1","doi-asserted-by":"crossref","first-page":"5917","DOI":"10.3390\/ijms25115917","article-title":"Targeted therapies for EGFR exon 20 insertion mutation in non-small-cell lung cancer","volume":"25","author":"Seo D","year":"2024","unstructured":"Seo D, Lim JH. Targeted therapies for EGFR exon 20 insertion mutation in non-small-cell lung cancer. Int J Mol Sci. 2024;25(11):5917.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"e_1_3_3_10_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1158\/1535-7163.MCT-12-0620","article-title":"EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics","volume":"12","author":"Arcila ME","year":"2013","unstructured":"Arcila ME, Nafa K, Chaft JE, Rekhtman N, Lau C, Reva BA, Zakowski MF, Kris MG, Ladanyi M. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220\u2013229.","journal-title":"Mol Cancer Ther"},{"issue":"7","key":"e_1_3_3_11_1","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1158\/2159-8290.CD-20-1683","article-title":"Mobocertinib (TAK-788): a targeted inhibitor of EGFR Exon 20 insertion mutants in non-small cell lung cancer","volume":"11","author":"Gonzalvez F","year":"2021","unstructured":"Gonzalvez F, Vincent S, Baker TE, Gould AE, Li S, Wardwell SD, Nadworny S, Ning Y, Zhang S, Huang W-S, et al. Mobocertinib (TAK-788): a targeted inhibitor of EGFR Exon 20 insertion mutants in non-small cell lung cancer. Cancer Discov. 2021;11(7):1672\u20131687.","journal-title":"Cancer Discov"},{"issue":"3","key":"e_1_3_3_12_1","doi-asserted-by":"crossref","first-page":"835","DOI":"10.4143\/crt.2017.303","article-title":"Phase 1 studies of poziotinib, an irreversible pan-HER tyrosine kinase inhibitor in patients with advanced solid tumors","volume":"50","author":"Kim TM","year":"2018","unstructured":"Kim TM, Lee K-W, Oh D-Y, Lee J-S, Im S-A, Kim D-W, Han S-W, Kim YJ, Kim T-Y, Kim JH, et al. Phase 1 studies of poziotinib, an irreversible pan-HER tyrosine kinase inhibitor in patients with advanced solid tumors. Cancer Res Treat. 2018;50(3):835\u2013842.","journal-title":"Cancer Res Treat"},{"issue":"7","key":"e_1_3_3_13_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1200\/JCO.21.01323","article-title":"Poziotinib in non-small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 Trial","volume":"40","author":"Le X","year":"2022","unstructured":"Le X, Cornelissen R, Garassino M, Clarke JM, Tchekmedyian N, Goldman JW, Leu S-Y, Bhat G, Lebel F, Heymach JV, et al. Poziotinib in non-small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 Trial. J Clin Oncol. 2022;40(7):710\u2013718. 2022","journal-title":"J Clin Oncol"},{"issue":"8","key":"e_1_3_3_14_1","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1158\/1535-7163.MCT-17-1206","article-title":"TAS6417, a novel EGFR inhibitor targeting exon 20 insertion mutations","volume":"17","author":"Hasako S","year":"2018","unstructured":"Hasako S, Terasaka M, Abe N, Uno T, Ohsawa H, Hashimoto A, Fujita R, Tanaka K, Okayama T, Wadhwa R, et al. TAS6417, a novel EGFR inhibitor targeting exon 20 insertion mutations. Mol Cancer Ther. 2018;17(8):1648\u20131658.","journal-title":"Mol Cancer Ther"},{"key":"e_1_3_3_15_1","unstructured":"Himmelsbach F Langkopf E Blech S Jung B Baum E Solca F. Quinazoline derivatives medicaments containing said compounds their utilization and method for the production thereof. WO. 02\/(50043 A1) June 27 2002."},{"key":"e_1_3_3_16_1","unstructured":"Breitenstein W Cowan-Jacob S Furet P et al. 2 4-Diamino-pyrimidine Derivatives as Tyrosine Kinase Inhibitors for the Treatment of Cancer and Viral Infections. WO. November 17 ;2005\/(107758 A1). 2005."},{"issue":"13","key":"e_1_3_3_17_1","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/j.bmc.2016.01.003","article-title":"Discovery of new [1,4]dioxino[2,3-f]quinazoline-based inhibitors of EGFR including the T790M\/L858R mutant","volume":"24","author":"Qin X","year":"2016","unstructured":"Qin X, Li Z, Yang L, Liu P, Hu L, Zeng C, Pan Z. Discovery of new [1,4]dioxino[2,3-f]quinazoline-based inhibitors of EGFR including the T790M\/L858R mutant. Bioorg Med Chem. 2016;24(13):2871\u20132881.","journal-title":"Bioorg Med Chem"},{"issue":"6","key":"e_1_3_3_18_1","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1021\/jm100087s","article-title":"Intramolecular hydrogen bonding in medicinal chemistry","volume":"53","author":"Kuhn B","year":"2010","unstructured":"Kuhn B, Mohr P, Stahl M. Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem. 2010;53(6):2601\u20132611.","journal-title":"J Med Chem"},{"issue":"7","key":"e_1_3_3_19_1","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1016\/j.bmc.2012.01.037","article-title":"Intramolecular hydrogen bonding: a potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase","volume":"20","author":"Labby KJ","year":"2012","unstructured":"Labby KJ, Xue F, Kraus JM, Ji H, Mataka J, Li H, Mart\u00e1sek P, Roman LJ, Poulos TL, Silverman RB, et al. Intramolecular hydrogen bonding: a potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem. 2012;20(7):2435\u20132443.","journal-title":"Bioorg Med Chem"},{"issue":"2","key":"e_1_3_3_20_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1039\/D0RA09995C","article-title":"The importance of intramolecular hydrogen bonds on the translocation of the small drug piracetam through a lipid bilayer","volume":"11","author":"Coimbra JTS","year":"2020","unstructured":"Coimbra JTS, Feghali R, Ribeiro RP, Ramos MJ, Fernandes PA. The importance of intramolecular hydrogen bonds on the translocation of the small drug piracetam through a lipid bilayer. RSC Adv. 2020;11(2):899\u2013908.","journal-title":"RSC Adv"},{"issue":"1","key":"e_1_3_3_21_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/jb\/mvy032","article-title":"Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody","volume":"164","author":"Miyanabe K","year":"2018","unstructured":"Miyanabe K, Akiba H, Kuroda D, Nakakido M, Kusano-Arai O, Iwanari H, Hamakubo T, Caaveiro JMM, Tsumoto K. Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody. J Biochem. 2018;164(1):65\u201376.","journal-title":"J Biochem"},{"issue":"10","key":"e_1_3_3_22_1","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.3390\/molecules25102314","article-title":"Methods to enhance the metabolic stability of peptide-based PET radiopharmaceuticals","volume":"25","author":"Evans BJ","year":"2020","unstructured":"Evans BJ, King AT, Katsifis A, Matesic L, Jamie JF. Methods to enhance the metabolic stability of peptide-based PET radiopharmaceuticals. Molecules. 2020;25(10):2314.","journal-title":"Molecules"},{"issue":"22","key":"e_1_3_3_23_1","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1021\/jm060434q","article-title":"N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src\/Abl kinase inhibitor","volume":"49","author":"Hennequin LF","year":"2006","unstructured":"Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A, et al. N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src\/Abl kinase inhibitor. J Med Chem. 2006;49(22):6465\u20136488.","journal-title":"J Med Chem"},{"key":"e_1_3_3_24_1","first-page":"4085","article-title":"Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs","volume":"77","author":"Chandra G","year":"2023","unstructured":"Chandra G, Singh DV, Mahato GK, Patel S. Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs. Chem Zvesti. 2023;77:4085\u20134106.","journal-title":"Chem Zvesti"},{"issue":"3","key":"e_1_3_3_25_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3390\/ph17030281","article-title":"The role of small molecules containing fluorine atoms in medicine and imaging applications","volume":"17","author":"Henary E","year":"2024","unstructured":"Henary E, Casa S, Dost TL, Sloop JC, Henary M. The role of small molecules containing fluorine atoms in medicine and imaging applications. Pharmaceuticals (Basel). 2024;17(3):281.","journal-title":"Pharmaceuticals (Basel)"}],"container-title":["Journal of Enzyme Inhibition and Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.tandfonline.com\/doi\/pdf\/10.1080\/14756366.2026.2730846","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.tandfonline.com\/doi\/full-xml\/10.1080\/14756366.2026.2730846","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.tandfonline.com\/doi\/pdf\/10.1080\/14756366.2026.2730846","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:38:33Z","timestamp":1790350713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.tandfonline.com\/doi\/full\/10.1080\/14756366.2026.2730846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12,31]]}},"alternative-id":["10.1080\/14756366.2026.2730846"],"URL":"https:\/\/doi.org\/10.1080\/14756366.2026.2730846","relation":{},"ISSN":["1475-6366","1475-6374"],"issn-type":[{"value":"1475-6366","type":"print"},{"value":"1475-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"The publishing and review policy for this title is described in its Aims & Scope.","order":1,"name":"peerreview_statement","label":"Peer Review Statement"},{"value":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ienz20","URL":"http:\/\/www.tandfonline.com\/action\/journalInformation?show=aimsScope&journalCode=ienz20","order":2,"name":"aims_and_scope_url","label":"Aim & Scope"},{"value":"2026-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-23","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2730846"}}