{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:19:16Z","timestamp":1787998756235,"version":"build-2784847793"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"crossref","award":["NSTC 108-2320-B-038-027-MY3"],"award-info":[{"award-number":["NSTC 108-2320-B-038-027-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"crossref","award":["NSTC 108-2320-B-038-027-MY3"],"award-info":[{"award-number":["NSTC 108-2320-B-038-027-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"crossref","award":["NSTC 110-2320-B-038-033-MY3"],"award-info":[{"award-number":["NSTC 110-2320-B-038-033-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"crossref","award":["NSTC 110-2320-B-038-033-MY3"],"award-info":[{"award-number":["NSTC 110-2320-B-038-033-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"crossref","award":["NSTC 108-2320-B-038-027-MY3"],"award-info":[{"award-number":["NSTC 108-2320-B-038-027-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC111-2320-B-038-032-MY3"],"award-info":[{"award-number":["NSTC111-2320-B-038-032-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC111-2320-B-038-032-MY3"],"award-info":[{"award-number":["NSTC111-2320-B-038-032-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC111-2320-B-038-032-MY3"],"award-info":[{"award-number":["NSTC111-2320-B-038-032-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010613","name":"Taipei Medical University Hospital","doi-asserted-by":"publisher","award":["111TMU-TMUH-02-1"],"award-info":[{"award-number":["111TMU-TMUH-02-1"]}],"id":[{"id":"10.13039\/501100010613","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010613","name":"Taipei Medical University Hospital","doi-asserted-by":"publisher","award":["111TMU-TMUH-02-1"],"award-info":[{"award-number":["111TMU-TMUH-02-1"]}],"id":[{"id":"10.13039\/501100010613","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-06543-3","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T11:21:10Z","timestamp":1751368870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hinokiflavone is a novel CK2 inhibitor promoting apoptosis and synergizing with chemotherapeutic agents in cisplatin resistant bladder cancer cells"],"prefix":"10.1038","volume":"15","author":[{"given":"Tsung-Han","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Pin","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Jyun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Cheng","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Han","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"6543_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229\u2013263. https:\/\/doi.org\/10.3322\/caac.21834 (2024).","journal-title":"CA Cancer J. Clin."},{"key":"6543_CR2","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1001\/jama.2020.17598","volume":"324","author":"AT Lenis","year":"2020","unstructured":"Lenis, A. T., Lec, P. M., Chamie, K. & Mshs, M. D. Bladder cancer: A review. JAMA 324, 1980\u20131991. https:\/\/doi.org\/10.1001\/jama.2020.17598 (2020).","journal-title":"JAMA"},{"key":"6543_CR3","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.eururo.2013.06.003","volume":"64","author":"M Babjuk","year":"2013","unstructured":"Babjuk, M. et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur. Urol. 64, 639\u2013653. https:\/\/doi.org\/10.1016\/j.eururo.2013.06.003 (2013).","journal-title":"Eur. Urol."},{"key":"6543_CR4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nrclinonc.2016.188","volume":"14","author":"SA Funt","year":"2017","unstructured":"Funt, S. A. & Rosenberg, J. E. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Nat. Rev. Clin. Oncol. 14, 221\u2013234. https:\/\/doi.org\/10.1038\/nrclinonc.2016.188 (2017).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"6543_CR5","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1097\/CCO.0000000000000064","volume":"26","author":"M Ghosh","year":"2014","unstructured":"Ghosh, M., Brancato, S. J., Agarwal, P. K. & Apolo, A. B. Targeted therapies in urothelial carcinoma. Curr. Opin. Oncol. 26, 305\u2013320. https:\/\/doi.org\/10.1097\/CCO.0000000000000064 (2014).","journal-title":"Curr. Opin. Oncol."},{"key":"6543_CR6","doi-asserted-by":"publisher","first-page":"5682078","DOI":"10.1155\/2018\/5682078","volume":"2018","author":"N Bukhari","year":"2018","unstructured":"Bukhari, N., Al-Shamsi, H. O. & Azam, F. Update on the treatment of metastatic urothelial carcinoma. ScientificWorldJournal 2018, 5682078. https:\/\/doi.org\/10.1155\/2018\/5682078 (2018).","journal-title":"ScientificWorldJournal"},{"key":"6543_CR7","doi-asserted-by":"publisher","unstructured":"Labadie, B. W., Balar, A. V. & Luke, J. J. Immune checkpoint inhibitors for genitourinary cancers: treatment indications, investigational approaches and biomarkers. Cancers (Basel). 13. https:\/\/doi.org\/10.3390\/cancers13215415 (2021).","DOI":"10.3390\/cancers13215415"},{"key":"6543_CR8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41585-019-0263-6","volume":"17","author":"J Afonso","year":"2020","unstructured":"Afonso, J., Santos, L. L., Longatto-Filho, A. & Baltazar, F. Competitive glucose metabolism as a target to boost bladder cancer immunotherapy. Nat. Rev. Urol. 17, 77\u2013106. https:\/\/doi.org\/10.1038\/s41585-019-0263-6 (2020).","journal-title":"Nat. Rev. Urol."},{"key":"6543_CR9","doi-asserted-by":"publisher","first-page":"7102","DOI":"10.3390\/app10207102","volume":"10","author":"M Scholtes","year":"2020","unstructured":"Scholtes, M. et al. Targeted therapy in metastatic bladder cancer: present status and future directions. Appl. Sci. 10, 7102 (2020).","journal-title":"Appl. Sci."},{"key":"6543_CR10","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1056\/NEJMoa2312117","volume":"390","author":"T Powles","year":"2024","unstructured":"Powles, T. et al. Enfortumab Vedotin and pembrolizumab in untreated advanced urothelial Cancer. N Engl. J. Med. 390, 875\u2013888. https:\/\/doi.org\/10.1056\/NEJMoa2312117 (2024).","journal-title":"N Engl. J. Med."},{"key":"6543_CR11","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2217\/fon-2023-0112","volume":"20","author":"CJ Hoimes","year":"2024","unstructured":"Hoimes, C. J. et al. A plain Language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab Vedotin plus pembrolizumab. Future Oncol. 20, 351\u2013360. https:\/\/doi.org\/10.2217\/fon-2023-0112 (2024).","journal-title":"Future Oncol."},{"key":"6543_CR12","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.6004\/jnccn.2018.0072","volume":"16","author":"TW Flaig","year":"2018","unstructured":"Flaig, T. W. et al. NCCN guidelines insights: bladder cancer, version 5.2018. J. Natl. Compr. Canc Netw. 16, 1041\u20131053. https:\/\/doi.org\/10.6004\/jnccn.2018.0072 (2018).","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"6543_CR13","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/onc.2011.384","volume":"31","author":"L Galluzzi","year":"2012","unstructured":"Galluzzi, L. et al. Molecular mechanisms of cisplatin resistance. Oncogene 31, 1869\u20131883. https:\/\/doi.org\/10.1038\/onc.2011.384 (2012).","journal-title":"Oncogene"},{"key":"6543_CR14","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1586\/era.11.201","volume":"12","author":"RM Drayton","year":"2012","unstructured":"Drayton, R. M. & Catto, J. W. Molecular mechanisms of cisplatin resistance in bladder cancer. Expert Rev. Anticancer Ther. 12, 271\u2013281. https:\/\/doi.org\/10.1586\/era.11.201 (2012).","journal-title":"Expert Rev. Anticancer Ther."},{"key":"6543_CR15","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1021\/np200906s","volume":"75","author":"DJ Newman","year":"2012","unstructured":"Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 75, 311\u2013335. https:\/\/doi.org\/10.1021\/np200906s (2012).","journal-title":"J. Nat. Prod."},{"key":"6543_CR16","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","volume":"83","author":"DJ Newman","year":"2020","unstructured":"Newman, D. J. & Cragg, G. M. Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019. J. Nat. Prod. 83, 770\u2013803. https:\/\/doi.org\/10.1021\/acs.jnatprod.9b01285 (2020).","journal-title":"J. Nat. Prod."},{"key":"6543_CR17","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1158\/1535-7163.MCT-09-0366","volume":"8","author":"EA Perez","year":"2009","unstructured":"Perez, E. A. Microtubule inhibitors: differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Mol. Cancer Ther. 8, 2086\u20132095. https:\/\/doi.org\/10.1158\/1535-7163.MCT-09-0366 (2009).","journal-title":"Mol. Cancer Ther."},{"key":"6543_CR18","doi-asserted-by":"publisher","first-page":"404","DOI":"10.3322\/caac.21631","volume":"70","author":"VG Patel","year":"2020","unstructured":"Patel, V. G., Oh, W. K. & Galsky, M. D. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J. Clin. 70, 404\u2013423. https:\/\/doi.org\/10.3322\/caac.21631 (2020).","journal-title":"CA Cancer J. Clin."},{"key":"6543_CR19","doi-asserted-by":"publisher","unstructured":"Kopustinskiene, D. M., Jakstas, V., Savickas, A. & Bernatoniene, J. Flavonoids as Anticancer Agents. Nutrients 12, (2020). https:\/\/doi.org\/10.3390\/nu12020457","DOI":"10.3390\/nu12020457"},{"key":"6543_CR20","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1017\/jns.2016.41","volume":"5","author":"AN Panche","year":"2016","unstructured":"Panche, A. N., Diwan, A. D. & Chandra, S. R. Flavonoids: an overview. J. Nutr. Sci. 5, e47. https:\/\/doi.org\/10.1017\/jns.2016.41 (2016).","journal-title":"J. Nutr. Sci."},{"key":"6543_CR21","doi-asserted-by":"publisher","first-page":"834","DOI":"10.2174\/1389557517666161104130026","volume":"17","author":"VS Gontijo","year":"2017","unstructured":"Gontijo, V. S., Dos Santos, M. H. & Viegas, C. Jr. Biological and chemical aspects of natural biflavonoids from plants: A brief review. Mini Rev. Med. Chem. 17, 834\u2013862. https:\/\/doi.org\/10.2174\/1389557517666161104130026 (2017).","journal-title":"Mini Rev. Med. Chem."},{"key":"6543_CR22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s13659-021-00298-w","volume":"11","author":"JF Goossens","year":"2021","unstructured":"Goossens, J. F., Goossens, L. & Bailly, C. Hinokiflavone and related C-O-C-Type biflavonoids as Anti-cancer compounds: properties and mechanism of action. Nat. Prod. Bioprospect. 11, 365\u2013377. https:\/\/doi.org\/10.1007\/s13659-021-00298-w (2021).","journal-title":"Nat. Prod. Bioprospect"},{"key":"6543_CR23","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1016\/j.bmc.2011.04.010","volume":"19","author":"G Sagrera","year":"2011","unstructured":"Sagrera, G., Bertucci, A., Vazquez, A. & Seoane, G. Synthesis and antifungal activities of natural and synthetic biflavonoids. Bioorg. Med. Chem. 19, 3060\u20133073. https:\/\/doi.org\/10.1016\/j.bmc.2011.04.010 (2011).","journal-title":"Bioorg. Med. Chem."},{"key":"6543_CR24","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.jep.2017.12.022","volume":"214","author":"S Lee","year":"2018","unstructured":"Lee, S. et al. Ameliorative effects of Juniperus rigida fruit on oxazolone- and 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice. J. Ethnopharmacol. 214, 160\u2013167. https:\/\/doi.org\/10.1016\/j.jep.2017.12.022 (2018).","journal-title":"J. Ethnopharmacol."},{"key":"6543_CR25","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jpba.2018.03.005","volume":"154","author":"B Zhuang","year":"2018","unstructured":"Zhuang, B. et al. Chemical profiling and quantitation of bioactive compounds in Platycladi cacumen by UPLC-Q-TOF-MS\/MS and UPLC-DAD. J. Pharm. Biomed. Anal. 154, 207\u2013215. https:\/\/doi.org\/10.1016\/j.jpba.2018.03.005 (2018).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"6543_CR26","doi-asserted-by":"publisher","unstructured":"Wang, G., Yao, S., Zhang, X. X. & Song, H. Rapid screening and structural characterization of antioxidants from the extract of Selaginella doederleinii Hieron with DPPH-UPLC-Q-TOF\/MS method. Int. J. Anal. Chem. 2015 (849769). https:\/\/doi.org\/10.1155\/2015\/849769 (2015).","DOI":"10.1155\/2015\/849769"},{"key":"6543_CR27","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s12272-001-1151-3","volume":"31","author":"HP Kim","year":"2008","unstructured":"Kim, H. P., Park, H., Son, K. H., Chang, H. W. & Kang, S. S. Biochemical Pharmacology of biflavonoids: implications for anti-inflammatory action. Arch. Pharm. Res. 31, 265\u2013273. https:\/\/doi.org\/10.1007\/s12272-001-1151-3 (2008).","journal-title":"Arch. Pharm. Res."},{"key":"6543_CR28","doi-asserted-by":"publisher","unstructured":"Shim, S. Y., Lee, S. G. & Lee, M. Biflavonoids isolated from Selaginella Tamariscina and their Anti-Inflammatory activities via ERK 1\/2 signaling. Molecules 23 https:\/\/doi.org\/10.3390\/molecules23040926 (2018).","DOI":"10.3390\/molecules23040926"},{"key":"6543_CR29","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1111\/jgh.14581","volume":"34","author":"J Zhou","year":"2019","unstructured":"Zhou, J. et al. Antitumor activity in colorectal cancer induced by Hinokiflavone. J. Gastroenterol. Hepatol. 34, 1571\u20131580. https:\/\/doi.org\/10.1111\/jgh.14581 (2019).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"6543_CR30","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/cbf.3443","volume":"38","author":"W Huang","year":"2020","unstructured":"Huang, W. et al. Hinokiflavone induces apoptosis and inhibits migration of breast cancer cells via EMT signalling pathway. Cell. Biochem. Funct. 38, 249\u2013256. https:\/\/doi.org\/10.1002\/cbf.3443 (2020).","journal-title":"Cell. Biochem. Funct."},{"key":"6543_CR31","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.21873\/invivo.11351","volume":"32","author":"KC Lee","year":"2018","unstructured":"Lee, K. C., Chen, W. T., Liu, Y. C., Lin, S. S. & Hsu, F. T. Amentoflavone inhibits hepatocellular carcinoma progression through blockage of ERK\/NF-kB activation. Vivo 32, 1097\u20131103. https:\/\/doi.org\/10.21873\/invivo.11351 (2018).","journal-title":"Vivo"},{"key":"6543_CR32","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1158\/1078-0432.CCR-17-2066","volume":"24","author":"CH Chen","year":"2018","unstructured":"Chen, C. H. et al. Dual Inhibition of PIK3C3 and FGFR as a new therapeutic approach to treat bladder Cancer. Clin. Cancer Res. 24, 1176\u20131189. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-2066 (2018).","journal-title":"Clin. Cancer Res."},{"key":"6543_CR33","doi-asserted-by":"publisher","first-page":"8798","DOI":"10.1021\/jf1020158","volume":"58","author":"CY Huang","year":"2010","unstructured":"Huang, C. Y. et al. Ling-Zhi polysaccharides potentiate cytotoxic effects of anticancer drugs against drug-resistant urothelial carcinoma cells. J. Agric. Food Chem. 58, 8798\u20138805. https:\/\/doi.org\/10.1021\/jf1020158 (2010).","journal-title":"J. Agric. Food Chem."},{"key":"6543_CR34","doi-asserted-by":"publisher","unstructured":"Chen, M. C., Lin, Y. C., Liao, Y. H., Liou, J. P. & Chen, C. H. MPT0G612, a novel HDAC6 inhibitor, induces apoptosis and suppresses IFN-gamma-Induced programmed Death-Ligand 1 in human colorectal carcinoma cells. Cancers (Basel). 11 https:\/\/doi.org\/10.3390\/cancers11101617 (2019).","DOI":"10.3390\/cancers11101617"},{"key":"6543_CR35","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41419-024-07298-x","volume":"15","author":"CC Tu","year":"2024","unstructured":"Tu, C. C. et al. Targeting PPARgamma via SIAH1\/2-mediated ubiquitin-proteasomal degradation as a new therapeutic approach in luminal-type bladder cancer. Cell. Death Dis. 15, 908. https:\/\/doi.org\/10.1038\/s41419-024-07298-x (2024).","journal-title":"Cell. Death Dis."},{"key":"6543_CR36","doi-asserted-by":"publisher","unstructured":"Chang, C. H. et al. Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy\/DAPK2\/Apoptosis Signaling Cascade. Mar Drugs 21, (2023). https:\/\/doi.org\/10.3390\/md21020073","DOI":"10.3390\/md21020073"},{"key":"6543_CR37","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U S A. 102, 15545\u201315550. https:\/\/doi.org\/10.1073\/pnas.0506580102 (2005).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"6543_CR38","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha, V. K. et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267\u2013273. https:\/\/doi.org\/10.1038\/ng1180 (2003).","journal-title":"Nat. Genet."},{"key":"6543_CR39","unstructured":"Schr\u00f6dinger Release 2022-3. Maestro, Schr\u00f6dinger, LLC, New York, NY, (2021)."},{"key":"6543_CR40","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The protein data bank. Nucleic Acids Res. 28, 235\u2013242. https:\/\/doi.org\/10.1093\/nar\/28.1.235 (2000).","journal-title":"Nucleic Acids Res."},{"key":"6543_CR41","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"RA Friesner","year":"2004","unstructured":"Friesner, R. A. et al. Glide: A new approach for rapid, accurate Docking and scoring. 1. Method and assessment of Docking accuracy. J. Med. Chem. 47, 1739\u20131749. https:\/\/doi.org\/10.1021\/jm0306430 (2004).","journal-title":"J. Med. Chem."},{"key":"6543_CR42","unstructured":"Biovia, D. S. Pipeline Pilot. Dassault Syst\u00e8mes (2021)."},{"key":"6543_CR43","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.1021\/bi300531c","volume":"51","author":"G Lolli","year":"2012","unstructured":"Lolli, G. et al. Inhibition of protein kinase CK2 by flavonoids and tyrphostins. A structural insight. Biochemistry 51, 6097\u20136107. https:\/\/doi.org\/10.1021\/bi300531c (2012).","journal-title":"Biochemistry"},{"key":"6543_CR44","doi-asserted-by":"publisher","first-page":"109723","DOI":"10.1016\/j.mehy.2020.109723","volume":"141","author":"MF McCarty","year":"2020","unstructured":"McCarty, M. F., Assanga, S. I. & Lujan, L. L. Flavones and flavonols May have clinical potential as CK2 inhibitors in cancer therapy. Med. Hypotheses. 141, 109723. https:\/\/doi.org\/10.1016\/j.mehy.2020.109723 (2020).","journal-title":"Med. Hypotheses"},{"key":"6543_CR45","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1096\/fj.02-0473rev","volume":"17","author":"F Meggio","year":"2003","unstructured":"Meggio, F. & Pinna, L. A. One-thousand-and-one substrates of protein kinase CK2? FASEB J. 17, 349\u2013368. https:\/\/doi.org\/10.1096\/fj.02-0473rev (2003).","journal-title":"FASEB J."},{"key":"6543_CR46","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1002\/cbic.200700307","volume":"8","author":"R Battistutta","year":"2007","unstructured":"Battistutta, R. et al. The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules. ChemBioChem 8, 1804\u20131809. https:\/\/doi.org\/10.1002\/cbic.200700307 (2007).","journal-title":"ChemBioChem"},{"key":"6543_CR47","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/sj.cdd.4401604","volume":"12","author":"G Di Maira","year":"2005","unstructured":"Di Maira, G. et al. Protein kinase CK2 phosphorylates and upregulates akt\/pkb. Cell. Death Differ. 12, 668\u2013677. https:\/\/doi.org\/10.1038\/sj.cdd.4401604 (2005).","journal-title":"Cell. Death Differ."},{"key":"6543_CR48","doi-asserted-by":"publisher","first-page":"3363","DOI":"10.1007\/s00018-009-0108-1","volume":"66","author":"G Di Maira","year":"2009","unstructured":"Di Maira, G., Brustolon, F., Pinna, L. A. & Ruzzene, M. Dephosphorylation and inactivation of akt\/pkb is counteracted by protein kinase CK2 in HEK 293T cells. Cell. Mol. Life Sci. 66, 3363\u20133373. https:\/\/doi.org\/10.1007\/s00018-009-0108-1 (2009).","journal-title":"Cell. Mol. Life Sci."},{"key":"6543_CR49","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1158\/1541-7786.MCR-16-0291","volume":"15","author":"U Rozovski","year":"2017","unstructured":"Rozovski, U. et al. Constitutive phosphorylation of STAT3 by the CK2-BLNK-CD5 complex. Mol. Cancer Res. 15, 610\u2013618. https:\/\/doi.org\/10.1158\/1541-7786.MCR-16-0291 (2017).","journal-title":"Mol. Cancer Res."},{"key":"6543_CR50","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.dnarep.2010.04.008","volume":"9","author":"JL Parsons","year":"2010","unstructured":"Parsons, J. L. et al. XRCC1 phosphorylation by CK2 is required for its stability and efficient DNA repair. DNA Repair. (Amst). 9, 835\u2013841. https:\/\/doi.org\/10.1016\/j.dnarep.2010.04.008 (2010).","journal-title":"DNA Repair. (Amst)"},{"key":"6543_CR51","doi-asserted-by":"publisher","first-page":"10288","DOI":"10.1158\/0008-5472.CAN-10-1893","volume":"70","author":"A Siddiqui-Jain","year":"2010","unstructured":"Siddiqui-Jain, A. et al. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy. Cancer Res. 70, 10288\u201310298. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-1893 (2010).","journal-title":"Cancer Res."},{"key":"6543_CR52","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1080\/10717544.2020.1748760","volume":"27","author":"Y Chen","year":"2020","unstructured":"Chen, Y., Feng, X., Li, L., Song, K. & Zhang, L. Preparation and antitumor evaluation of Hinokiflavone hybrid micelles with mitochondria targeted for lung adenocarcinoma treatment. Drug Deliv. 27, 565\u2013574. https:\/\/doi.org\/10.1080\/10717544.2020.1748760 (2020).","journal-title":"Drug Deliv"},{"key":"6543_CR53","doi-asserted-by":"publisher","unstructured":"Pawellek, A. et al. Characterisation of the biflavonoid Hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP. Elife 6 https:\/\/doi.org\/10.7554\/eLife.27402 (2017).","DOI":"10.7554\/eLife.27402"},{"key":"6543_CR54","doi-asserted-by":"publisher","first-page":"105525","DOI":"10.1016\/j.phrs.2021.105525","volume":"167","author":"J Menezes","year":"2021","unstructured":"Menezes, J. & Diederich, M. F. Bioactivity of natural biflavonoids in metabolism-related disease and cancer therapies. Pharmacol. Res. 167, 105525. https:\/\/doi.org\/10.1016\/j.phrs.2021.105525 (2021).","journal-title":"Pharmacol. Res."},{"key":"6543_CR55","doi-asserted-by":"publisher","first-page":"4163","DOI":"10.1021\/acs.jmedchem.1c00079","volume":"64","author":"Y Wang","year":"2021","unstructured":"Wang, Y., Wang, X., Xu, G. & Gou, S. Novel CK2-Specific Pt(II) compound reverses Cisplatin-Induced resistance by inhibiting Cancer cell stemness and suppressing DNA damage repair in Non-small cell lung Cancer treatments. J. Med. Chem. 64, 4163\u20134178. https:\/\/doi.org\/10.1021\/acs.jmedchem.1c00079 (2021).","journal-title":"J. Med. Chem."},{"key":"6543_CR56","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.3892\/ol.2019.10696","volume":"18","author":"C Jin","year":"2019","unstructured":"Jin, C., Song, P. & Pang, J. The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549\/DDP human lung adenocarcinoma cell line. Oncol. Lett. 18, 3845\u20133856. https:\/\/doi.org\/10.3892\/ol.2019.10696 (2019).","journal-title":"Oncol. Lett."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06543-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06543-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06543-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T11:21:12Z","timestamp":1751368872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-06543-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6543"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-06543-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"22 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2025","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":"All Authors gave their consent to submit and publish the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"20922"}}