{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:21:48Z","timestamp":1790990508863,"version":"4.1.0"},"reference-count":61,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","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":[[2025,4]]},"DOI":"10.1016\/j.ejmech.2025.117328","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T10:02:24Z","timestamp":1738490544000},"page":"117328","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma"],"prefix":"10.1016","volume":"287","author":[{"given":"Xiao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Ru","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Bo","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4395-8879","authenticated-orcid":false,"given":"Sai-Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.117328_bib1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/0955-0674(94)90097-3","article-title":"Focal adhesion kinase and associated proteins","volume":"6","author":"Schaller","year":"1994","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.ejmech.2025.117328_bib2","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.cell.2007.05.041","article-title":"Structural basis for the autoinhibition of focal adhesion kinase","volume":"129","author":"Lietha","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2025.117328_bib3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s40164-023-00446-7","article-title":"Focal adhesion kinase: from biological functions to therapeutic strategies","volume":"12","author":"Tan","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"10.1016\/j.ejmech.2025.117328_bib4","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1242\/jcs.045112","article-title":"Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions","volume":"123","author":"Schaller","year":"2010","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ejmech.2025.117328_bib5","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nrc3792","article-title":"FAK in cancer: mechanistic findings and clinical applications","volume":"14","author":"Sulzmaier","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2025.117328_bib6","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ccell.2015.03.008","article-title":"Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin \u03b21\/FAK signaling","volume":"27","author":"Hirata","year":"2015","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejmech.2025.117328_bib7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2014.10.001","article-title":"FAK signaling in human cancer as a target for therapeutics","volume":"146","author":"Lee","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.ejmech.2025.117328_bib8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41568-021-00340-6","article-title":"Targeting FAK in anticancer combination therapies","volume":"21","author":"Dawson","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2025.117328_bib9","doi-asserted-by":"crossref","first-page":"974","DOI":"10.3892\/ol.2020.11612","article-title":"Expression of ASAP1 and FAK in gastric cancer and its clinicopathological significance","volume":"20","author":"Luo","year":"2020","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.ejmech.2025.117328_bib10","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.canlet.2020.10.005","article-title":"Focal adhesion kinase: insight into its roles and therapeutic potential in oesophageal cancer","volume":"496","author":"Zhang","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ejmech.2025.117328_bib11","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031726","article-title":"FAK in cancer: from mechanisms to therapeutic strategies","volume":"23","author":"Chuang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2025.117328_bib12","first-page":"2586","article-title":"Clinical significance of focal adhesion kinase (FAK) in cervical cancer progression and metastasis","volume":"13","author":"Chen","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"10.1016\/j.ejmech.2025.117328_bib13","doi-asserted-by":"crossref","first-page":"14382","DOI":"10.1021\/acs.jmedchem.0c01248","article-title":"Progress in the development of small molecular inhibitors of focal adhesion kinase (FAK)","volume":"63","author":"Lu","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib14","article-title":"FAK downregulation suppresses stem-like properties and migration of human colorectal cancer cells","volume":"18","author":"Xu","year":"2023","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.117328_bib15","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.21873\/anticanres.14494","article-title":"New imidazo[2,1-<em>b<\/em>][1,3,4]Thiadiazole derivatives inhibit FAK phosphorylation and potentiate the antiproliferative effects of gemcitabine through modulation of the human equilibrative nucleoside transporter-1 in peritoneal mesothelioma","volume":"40","author":"Li Petri","year":"2020","journal-title":"Anticancer Res."},{"key":"10.1016\/j.ejmech.2025.117328_bib16","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1080\/1061186X.2024.2385557","article-title":"Exploring the therapeutic potential of a novel series of imidazothiadiazoles targeting focal adhesion kinase (FAK) for pancreatic cancer treatment: synthesis, mechanistic insights and promising antitumor and safety profile","volume":"32","author":"Pecoraro","year":"2024","journal-title":"J. Drug Target."},{"key":"10.1016\/j.ejmech.2025.117328_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116678","article-title":"Targeting focal adhesion kinase (FAK) in cancer therapy: a recent update on inhibitors and PROTAC degraders","volume":"276","author":"Wang","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib18","doi-asserted-by":"crossref","first-page":"7478","DOI":"10.1021\/acs.jmedchem.6b00487","article-title":"Discovery of clinical candidate CEP-37440, a selective inhibitor of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK)","volume":"59","author":"Ott","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib19","doi-asserted-by":"crossref","first-page":"12707","DOI":"10.1021\/acs.jmedchem.0c01059","article-title":"Design, synthesis, and biological evaluation of covalent inhibitors of focal adhesion kinase (FAK) against human malignant glioblastoma","volume":"63","author":"Li","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib20","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1021\/acs.jmedchem.1c00459","article-title":"Identification of thieno[3,2-d]pyrimidine derivatives as dual inhibitors of focal adhesion kinase and FMS-like tyrosine kinase 3","volume":"64","author":"Cho","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115192","article-title":"Design, synthesis and evaluation of nitric oxide releasing derivatives of 2,4-diaminopyrimidine as novel FAK inhibitors for intervention of metastatic triple-negative breast cancer","volume":"250","author":"Zhang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114373","article-title":"Identification of novel and potent PROTACs targeting FAK for non-small cell lung cancer: Design, synthesis, and biological study","volume":"237","author":"Sun","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113978","article-title":"Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer","volume":"228","author":"Wei","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib24","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejmech.2019.04.004","article-title":"Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells","volume":"172","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2023.106895","article-title":"Design, synthesis and biological evaluation of novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors of FAK with potent anti-gastric cancer activities","volume":"141","author":"Liu","year":"2023","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.105790","article-title":"Design, synthesis and biological evaluation of novel FAK inhibitors with better selectivity over IR than TAE226","volume":"124","author":"Chen","year":"2022","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107134","article-title":"Discovery of 2,4-diarylaminopyrimidine derivatives bearing sulfonamide moiety as novel FAK inhibitors","volume":"144","author":"Li","year":"2024","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib28","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.yexcr.2011.02.008","article-title":"Anti-tumor effect in human breast cancer by TAE226, a dual inhibitor for FAK and IGF-IR in vitro and in vivo","volume":"317","author":"Kurio","year":"2011","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ejmech.2025.117328_bib29","first-page":"1473","article-title":"TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells","volume":"20","author":"Wang","year":"2008","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejmech.2025.117328_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0003800","article-title":"Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation","volume":"3","author":"Lietha","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2025.117328_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.106328","article-title":"The dual FAK-HDAC inhibitor MY-1259 displays potent activities in gastric cancers in vitro and in vivo","volume":"131","author":"Song","year":"2023","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2023.106713","article-title":"Discovery of novel pyrrolo [2,3-d] pyrimidine derivatives as potent FAK inhibitors based on cyclization strategy","volume":"139","author":"Zeng","year":"2023","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116913","article-title":"Development of novel focal adhesion kinase (FAK) inhibitors for targeting cancer: structural insights and therapeutic potential","volume":"279","author":"Li","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib34","first-page":"1","article-title":"Prospects of focal adhesion kinase inhibitors as a cancer therapy in preclinical and early phase study","author":"Gao","year":"2024","journal-title":"Expet Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2025.117328_bib35","article-title":"Roles and inhibitors of FAK in cancer: current advances and future directions","volume":"15","author":"Hu","year":"2024","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2025.117328_bib36","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/13543784.2020.1740680","article-title":"FAK-targeted and combination therapies for the treatment of cancer: an overview of phase I and II clinical trials","volume":"29","author":"Mohanty","year":"2020","journal-title":"Expet Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2025.117328_bib37","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1158\/1535-7163.MCT-06-0476","article-title":"Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo","volume":"6","author":"Liu","year":"2007","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2025.117328_bib38","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1158\/1078-0432.CCR-07-4755","article-title":"Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo","volume":"14","author":"Watanabe","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2025.117328_bib39","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1021\/acs.jmedchem.9b01541","article-title":"Urea derivatives in modern drug discovery and medicinal chemistry","volume":"63","author":"Ghosh","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib40","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1021\/jm020057r","article-title":"Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate","volume":"45","author":"Regan","year":"2002","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib41","doi-asserted-by":"crossref","first-page":"622","DOI":"10.2174\/0929867323666161129124915","article-title":"Ureas: applications in drug Design","volume":"24","author":"Jagtap","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib42","doi-asserted-by":"crossref","first-page":"7176","DOI":"10.1021\/acs.jmedchem.4c00023","article-title":"Discovery of urea derivatives of celastrol as selective peroxiredoxin 1 inhibitors against colorectal cancer cells","volume":"67","author":"Li","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117328_bib43","series-title":"Profiles of Drug Substances, Excipients and Related Methodology","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/bs.podrm.2018.11.003","article-title":"Chapter four - sorafenib","author":"Abdelgalil","year":"2019"},{"key":"10.1016\/j.ejmech.2025.117328_bib44","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.ejmech.2025.117328_bib45","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1021\/ml4000657","article-title":"Discovery of RG7112: a small-molecule MDM2 inhibitor in clinical development","volume":"4","author":"Vu","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2025.117328_bib46","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"10.1016\/j.ejmech.2025.117328_bib47","article-title":"Advances in diagnosis and management of cancer of the esophagus","volume":"385","author":"Deboever","year":"2024","journal-title":"Bmj"},{"key":"10.1016\/j.ejmech.2025.117328_bib48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/01.JAA.0001007328.84376.da","article-title":"Esophageal cancer: treatment advances and need for screening","volume":"37","author":"Eisner","year":"2024","journal-title":"Jaapa"},{"key":"10.1016\/j.ejmech.2025.117328_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.cclet.2024.110456","article-title":"New techniques and strategies in drug discovery (2020\u20132024 update)","volume":"36","author":"Gong","year":"2025","journal-title":"Chin. Chem. Lett."},{"key":"10.1016\/j.ejmech.2025.117328_bib50","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/sj.bjc.6601050","article-title":"FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma","volume":"89","author":"Miyazaki","year":"2003","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.ejmech.2025.117328_bib51","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.canlet.2020.10.005","article-title":"Focal adhesion kinase: insight into its roles and therapeutic potential in oesophageal cancer","volume":"496","author":"Zhang","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ejmech.2025.117328_bib52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41388-022-02568-4","article-title":"Phosphohistidine signaling promotes FAK-RB1 interaction and growth factor-independent proliferation of esophageal squamous cell carcinoma","volume":"42","author":"Zhang","year":"2023","journal-title":"Oncogene"},{"key":"10.1016\/j.ejmech.2025.117328_bib53","doi-asserted-by":"crossref","first-page":"77468","DOI":"10.18632\/oncotarget.12684","article-title":"MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK\/MAPK signaling pathway","volume":"7","author":"Cao","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejmech.2025.117328_bib54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13058-020-01298-3","article-title":"FAK activates AKT-mTOR signaling to promote the growth and progression of MMTV-Wnt1-driven basal-like mammary tumors","volume":"22","author":"Paul","year":"2020","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.ejmech.2025.117328_bib55","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.devcel.2010.09.011","article-title":"The hippo signaling pathway in development and cancer","volume":"19","author":"Pan","year":"2010","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ejmech.2025.117328_bib56","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nrc3458","article-title":"The Hippo pathway and human cancer","volume":"13","author":"Harvey","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2025.117328_bib57","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/s41392-022-01191-9","article-title":"The Hippo signalling pathway and its implications in human health and diseases","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.ejmech.2025.117328_bib58","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2024.130037","article-title":"YAP induces FAK phosphorylation to inhibit gastric cancer cell proliferation via upregulation of HMGB1","volume":"262","author":"Jiang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejmech.2025.117328_bib59","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.jhep.2021.05.018","article-title":"Focal adhesion kinase (FAK) promotes cholangiocarcinoma development and progression via YAP activation","volume":"75","author":"Song","year":"2021","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ejmech.2025.117328_bib60","article-title":"Focal adhesion kinase (FAK) inhibition synergizes with KRAS G12C inhibitors in treating cancer through the regulation of the FAK-YAP signaling","volume":"8","author":"Zhang","year":"2021","journal-title":"Adv. Sci."},{"key":"10.1016\/j.ejmech.2025.117328_bib61","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s00432-021-03604-8","article-title":"A review: hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression","volume":"147","author":"Li","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425000935?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425000935?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T06:07:37Z","timestamp":1759298857000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425000935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":61,"alternative-id":["S0223523425000935"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117328","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117328","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117328"}}