{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T05:36:05Z","timestamp":1777181765671,"version":"3.51.4"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":42,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-42845-w","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:23:11Z","timestamp":1773213791000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["X-ray crystal structure and in silico investigation of Tetrabromo thia-bridged diquinoline including anticancer mechanisms via target prediction and molecular docking"],"prefix":"10.1038","volume":"16","author":[{"given":"Solhe F.","family":"Alshahateet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghassab M.","family":"Al-Mazaideh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah A.","family":"Al-Trawneh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir A.","family":"Al-Taweel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shehdeh","family":"Jodeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"issue":"5","key":"42845_CR1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s002390010043","volume":"50","author":"RA Stein","year":"2000","unstructured":"Stein, R. A. & Staros, J. V. Evolutionary analysis of the ErbB receptor and ligand families. J. Mol. Evol. 50 (5), 397\u2013412 (2000).","journal-title":"J. Mol. Evol."},{"issue":"6924","key":"42845_CR2","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/nature01392","volume":"421","author":"HS Cho","year":"2003","unstructured":"Cho, H. S. et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421 (6924), 756\u2013760 (2003).","journal-title":"Nature"},{"issue":"2","key":"42845_CR3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/S1097-2765(03)00048-0","volume":"11","author":"TP Garrett","year":"2003","unstructured":"Garrett, T. P. et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell. 11 (2), 495\u2013505 (2003).","journal-title":"Mol. Cell."},{"key":"42845_CR4","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1093\/emboj\/16.7.1647","volume":"16","author":"D Graus-Porta","year":"1997","unstructured":"Graus-Porta, D. et al. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 16, 1647\u20131655 (1997).","journal-title":"EMBO J."},{"key":"42845_CR5","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1002\/j.1460-2075.1996.tb00603.x","volume":"15","author":"R Pinkas-Kramarski","year":"1996","unstructured":"Pinkas-Kramarski, R. et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J. 15, 2452\u20132467 (1996).","journal-title":"EMBO J."},{"issue":"10","key":"42845_CR6","doi-asserted-by":"publisher","first-page":"5770","DOI":"10.1128\/MCB.15.10.5770","volume":"15","author":"DJ Riese IInd","year":"1995","unstructured":"Riese IInd, D. J. et al. The cellular response to neuregulins is governed by complex interactions of the erbB receptor family. Mol. Cell. Biol. 15 (10), 5770\u20135776 (1995).","journal-title":"Mol. Cell. Biol."},{"key":"42845_CR7","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/j.1460-2075.1996.tb00356.x","volume":"15","author":"D Karunagaran","year":"1996","unstructured":"Karunagaran, D. et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J. 15, 254\u2013264 (1996).","journal-title":"EMBO J."},{"issue":"2\u20133","key":"42845_CR8","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/S0014-5793(99)00283-5","volume":"447","author":"JT Jones","year":"1999","unstructured":"Jones, J. T., Akita, R. W. & Sliwkowski, M. X. Binding specificities and affinities of egf domains for ErbB receptors. FEBS Lett. 447 (2\u20133), 227\u2013231 (1999).","journal-title":"FEBS Lett."},{"issue":"4905","key":"42845_CR9","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1126\/science.2470152","volume":"244","author":"DJ Slamon","year":"1989","unstructured":"Slamon, D. J. et al. Studies of the HER-2\/neu proto-oncogene in human breast and ovarian cancer. Science 244 (4905), 707\u2013712 (1989).","journal-title":"Science"},{"issue":"1","key":"42845_CR10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/bjc.1991.243","volume":"64","author":"NR Lemoine","year":"1991","unstructured":"Lemoine, N. R. et al. Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br. J. Cancer. 64 (1), 79\u201383 (1991).","journal-title":"Br. J. Cancer"},{"issue":"10 Suppl","key":"42845_CR11","first-page":"2199","volume":"53","author":"G Sauter","year":"1993","unstructured":"Sauter, G. et al. Heterogeneity of erbB-2 gene amplification in bladder cancer. Cancer Res. 53 (10 Suppl), 2199\u20132203 (1993).","journal-title":"Cancer Res."},{"issue":"2","key":"42845_CR12","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/gcc.2870030208","volume":"3","author":"G Stenman","year":"1991","unstructured":"Stenman, G. et al. Expression of the ERBB2 protein in benign and malignant salivary gland tumors. Genes Chromosomes Cancer. 3 (2), 128\u2013135 (1991).","journal-title":"Genes Chromosomes Cancer"},{"issue":"1","key":"42845_CR13","doi-asserted-by":"publisher","first-page":"508","DOI":"10.18632\/oncotarget.28747","volume":"16","author":"S Shyamsunder","year":"2025","unstructured":"Shyamsunder, S., Lu, Z., Takiar, V. & Waltz, S. E. Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: insights into RTK dependent and independent mechanisms. Oncotarget 16 (1), 508\u2013530 (2025).","journal-title":"Oncotarget"},{"key":"42845_CR14","doi-asserted-by":"crossref","unstructured":"Ramli, I. et al. Natural Products Targeting the EGFR\/HER2 Axis in Tumorigenesis: Interpretation of Molecular Mechanisms and Recent Insights Into Synergistic Strategies for Cancer Therapy (Food Frontiers, 2025).","DOI":"10.1002\/fft2.70135"},{"issue":"1","key":"42845_CR15","doi-asserted-by":"publisher","first-page":"127","DOI":"10.17509\/ijost.v11i2.89682","volume":"11","author":"Solhe Alshahateet","year":"2026","unstructured":"Alshahateet, S. F. et al. Structural characterization, hirshfield surface analysis, and molecular docking of novel diquinoline derivatives as anti-tumor agents. Indonesian J. Sci. Technol. 11 (1), 127\u2013148 (2026).","journal-title":"Indonesian J. Sci. Technol."},{"key":"42845_CR16","doi-asserted-by":"crossref","unstructured":"Mwaheb, M. A. et al. Versatile properties of Opuntia ficus-indica (L.) Mill. flowers: In vitro exploration of antioxidant, antimicrobial, and anticancer activities, network pharmacology analysis, and In-silico molecular docking simulation. Plos One. 19(11), e0313064 (2024).","DOI":"10.1371\/journal.pone.0313064"},{"issue":"2","key":"42845_CR17","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1080\/10406638.2024.2403544","volume":"45","author":"G Abouelenein","year":"2025","unstructured":"Abouelenein, G., El-boghdady, M. H., Ali, A. M., Said, A. Molecular investigations of novel pyrano [2, 3-c] pyrazole congeners as potential HCoV-229E inhibitors: synthesis, molecular modeling, 3D QSAR, and ADMET screening. Polycycl. Aromat. Compd. 45 (2), 251\u2013268 (2025).","journal-title":"Polycycl. Aromat. Compd."},{"issue":"7","key":"42845_CR18","doi-asserted-by":"publisher","first-page":"328","DOI":"10.3390\/md22070328","volume":"22","author":"SO Hassanin","year":"2024","unstructured":"Hassanin, S. O. et al. Combining in vitro, in vivo, and network pharmacology assays to identify targets and molecular mechanisms of spirulina-derived biomolecules against breast cancer. Mar. Drugs. 22 (7), 328 (2024).","journal-title":"Mar. Drugs"},{"key":"42845_CR19","doi-asserted-by":"publisher","first-page":"105971","DOI":"10.1016\/j.fitote.2024.105971","volume":"175","author":"NM Saeed","year":"2024","unstructured":"Saeed, N. M. et al. Exploring the anti-osteoporosis potential of Petroselinum crispum (Mill.) Fuss extract employing experimentally ovariectomized rat model and network pharmacology approach. Fitoterapia 175, 105971 (2024).","journal-title":"Fitoterapia"},{"key":"42845_CR20","doi-asserted-by":"publisher","first-page":"105744","DOI":"10.1016\/j.ejps.2021.105744","volume":"160","author":"MA Said","year":"2021","unstructured":"Said, M. A., Albohy, A., Abdelrahman, M. A. & Ibrahim, H. S. Importance of glutamine 189 flexibility in SARS-CoV-2 main protease: lesson learned from in silico virtual screening of ChEMBL database and molecular dynamics. Eur. J. Pharm. Sci. 160, 105744 (2021).","journal-title":"Eur. J. Pharm. Sci."},{"key":"42845_CR21","doi-asserted-by":"crossref","unstructured":"Ali, H. M., Said, M. A., Allam, S., Abdel-Aziz, H. A. & Abou-Seri, S. M. Exploring the antiproliferative and proapoptotic activities of new pyridopyrimidine derivatives and their analogs Vol. 118, 118053 (Bioorganic & Medicinal Chemistry, 2025).","DOI":"10.1016\/j.bmc.2024.118053"},{"issue":"3","key":"42845_CR22","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3390\/ph18030421","volume":"18","author":"K Zarif Attalla","year":"2025","unstructured":"Zarif Attalla, K. et al. Enhanced intranasal delivery of atorvastatin via superparamagnetic iron-oxide-loaded nanocarriers: cytotoxicity and inflammation evaluation and in vivo, in silico, and network pharmacology study for targeting glioblastoma management. Pharmaceuticals 18 (3), 421 (2025).","journal-title":"Pharmaceuticals"},{"key":"42845_CR23","doi-asserted-by":"publisher","first-page":"9111","DOI":"10.1039\/C5CE01838B","volume":"17","author":"SF Alshahateet","year":"2015","unstructured":"Alshahateet, S. F., Bhadbhade, M. M., Bishop, R., Craig andv, D. C. & Scudder, M. L. Halogen containing clusters N2Br2, N2Br4, S2Br4 and S2Br6 yield penannular inclusion compounds. CrystEngComm 17, 9111 (2015).","journal-title":"CrystEngComm"},{"key":"42845_CR24","doi-asserted-by":"crossref","unstructured":"Cheng, C. C. & Yan, S. J. in Organic reactions. The Friedl\u00fcnder Synthesis of Quinolines. Vol. 28, 37 (eds Dauben, W. C.) (J. Wiley & Sons, 1982).","DOI":"10.1002\/0471264180.or028.02"},{"issue":"01","key":"42845_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1055\/s-1992-21249","volume":"1992","author":"R Thummel","year":"1992","unstructured":"Thummel, R. The application of Friedl\u00e4nder and Fischer methodologies to the synthesis of organized polyaza cavities. Synlett 1992 (01), 1\u201312 (1992).","journal-title":"Synlett"},{"key":"42845_CR26","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/0471264180.os070.14","volume":"70","author":"R Bishop","year":"2003","unstructured":"Bishop, R. 9-Thiabicyclo [3.3. 1] Nonane-2. 6-dione Org. Syntheses. 70, 120\u2013120 (2003).","journal-title":"6-dione Org. Syntheses"},{"key":"42845_CR27","unstructured":"Bishop, R. Synth. Coll 692 (IX, 1998)."},{"key":"42845_CR28","unstructured":"Sheldrick, M. & SADABS Software for Empirical Absorption Correction (University of G\u00f6ttingen, 1996)."},{"key":"42845_CR29","unstructured":"SHELXTL Reference Manuals. Version 5.03, Siemens Energy and Automation, Inc., Analytical Instrumentation, Madison, WI. (1996)."},{"key":"42845_CR30","unstructured":"SMART and SAINT Software Reference Manuals. Version 4.0, Siemens Energy and Automation, Inc. Analytical Instrumentation, Madison (1996)."},{"key":"42845_CR31","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","volume":"53","author":"M Kanehisa","year":"2025","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: biological systems database as a model of the real world. Nucleic Acids Res. 53, D672\u2013D677 (2025).","journal-title":"Nucleic Acids Res."},{"key":"42845_CR32","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"42845_CR33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330 (2000).","journal-title":"Nucleic Acids Res."},{"key":"42845_CR34","unstructured":"www.kegg.jp\/kegg\/kegg1.html"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-42845-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-42845-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-42845-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T05:02:31Z","timestamp":1777179751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-42845-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["42845"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-42845-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"assertion":[{"value":"11 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and\/or the editor(s), and\/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}],"article-number":"13094"}}