{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:13:17Z","timestamp":1778159597598,"version":"3.51.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100011581","name":"IITI","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011581","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"DOI":"10.1007\/s10787-025-01786-y","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:05:52Z","timestamp":1749719152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A thioridazine-derived molecule exhibits potential anti-inflammatory activity through IKK inhibition"],"prefix":"10.1007","author":[{"given":"Shivmuni","family":"Sarup","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajat","family":"Atre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Obukhov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shams","family":"Tabrez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aravind Singh","family":"Kshatri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Hassan","family":"Sk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz","family":"Alamri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Shahnawaz","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-7130","authenticated-orcid":false,"given":"Mirza S","family":"Baig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"1786_CR1","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.3390\/cimb45020093","volume":"45","author":"A Alghamdi","year":"2023","unstructured":"Alghamdi A, Abouzied AS, Alamri A et al (2023) Synthesis, molecular docking, and dynamic simulation targeting main protease (Mpro) of new, thiazole clubbed pyridine scaffolds as potential COVID-19 inhibitors. Curr Issues Mol Biol 45:1422\u20131442. https:\/\/doi.org\/10.3390\/cimb45020093","journal-title":"Curr Issues Mol Biol"},{"key":"1786_CR2","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10555-005-1579-7","volume":"24","author":"KI Amiri","year":"2005","unstructured":"Amiri KI, Richmond A (2005) Role of nuclear factor-\u03ba B in melanoma. Cancer Metastasis Rev 24:301\u2013313. https:\/\/doi.org\/10.1007\/s10555-005-1579-7","journal-title":"Cancer Metastasis Rev"},{"key":"1786_CR3","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.str.2020.12.007","volume":"29","author":"T Asai","year":"2021","unstructured":"Asai T, Adachi N, Moriya T et al (2021) Cryo-EM structure of K+-Bound hERG channel complexed with the blocker astemizole. Structure 29:203-212.e4. https:\/\/doi.org\/10.1016\/j.str.2020.12.007","journal-title":"Structure"},{"key":"1786_CR4","doi-asserted-by":"publisher","first-page":"12471","DOI":"10.1038\/s41598-018-30763-5","volume":"8","author":"MS Baig","year":"2018","unstructured":"Baig MS, Roy A, Saqib U et al (2018) Repurposing thioridazine (TDZ) as an anti-inflammatory agent. Sci Rep 8:12471. https:\/\/doi.org\/10.1038\/s41598-018-30763-5","journal-title":"Sci Rep"},{"key":"1786_CR5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-3-13","volume":"3","author":"EE Bolton","year":"2011","unstructured":"Bolton EE, Kim S, Bryant SH (2011) PubChem3D: similar conformers. J Cheminform 3:13. https:\/\/doi.org\/10.1186\/1758-2946-3-13","journal-title":"J Cheminform"},{"key":"1786_CR6","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1073\/pnas.90.6.2532","volume":"90","author":"K Brown","year":"1993","unstructured":"Brown K, Park S, Kanno T et al (1993) Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci 90:2532\u20132536. https:\/\/doi.org\/10.1073\/pnas.90.6.2532","journal-title":"Proc Natl Acad Sci"},{"key":"1786_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e01429","volume":"5","author":"A Butler","year":"2019","unstructured":"Butler A, Zhang Y, Stuart AG et al (2019) Functional and pharmacological characterization of an S5 domain hERG mutation associated with short QT syndrome. Heliyon 5:e01429. https:\/\/doi.org\/10.1016\/j.heliyon.2019.e01429","journal-title":"Heliyon"},{"key":"1786_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.coi.2012.12.005","volume":"25","author":"J Chen","year":"2013","unstructured":"Chen J, Chen ZJ (2013) Regulation of NF-\u03baB by ubiquitination. Curr Opin Immunol 25:4\u201312. https:\/\/doi.org\/10.1016\/j.coi.2012.12.005","journal-title":"Curr Opin Immunol"},{"key":"1786_CR9","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature01322","volume":"420","author":"LM Coussens","year":"2002","unstructured":"Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860\u2013867. https:\/\/doi.org\/10.1038\/nature01322","journal-title":"Nature"},{"key":"1786_CR10","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1021\/ci400707h","volume":"54","author":"CE Dempsey","year":"2014","unstructured":"Dempsey CE, Wright D, Colenso CK et al (2014) Assessing hERG pore models as templates for drug docking using published experimental constraints: the inactivated state in the context of drug block. J Chem Inf Model 54:601\u2013612. https:\/\/doi.org\/10.1021\/ci400707h","journal-title":"J Chem Inf Model"},{"key":"1786_CR11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.2174\/1568010023344706","volume":"1","author":"BSP Fei Chen","year":"2002","unstructured":"Fei Chen BSP, Demers LM, BSP, Xianglin Shi BSP, (2002) Upstream signal transduction of NF-\u03baB activation. Curr Drug Target -Inflamm Allergy 1:137\u2013149. https:\/\/doi.org\/10.2174\/1568010023344706","journal-title":"Curr Drug Target -Inflamm Allergy"},{"key":"1786_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1214095","author":"C Guldenpfennig","year":"2023","unstructured":"Guldenpfennig C, Teixeiro E, Daniels M (2023) NF-kB\u2019s contribution to B cell fate decisions. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2023.1214095","journal-title":"Front Immunol"},{"key":"1786_CR13","doi-asserted-by":"publisher","first-page":"16s","DOI":"10.1183\/09031936.03.00000503a","volume":"22","author":"G Haegeman","year":"2003","unstructured":"Haegeman G (2003) Inhibition of signal transduction pathways involved in inflammation. Eur Respir J 22:16s\u201319s. https:\/\/doi.org\/10.1183\/09031936.03.00000503a","journal-title":"Eur Respir J"},{"key":"1786_CR14","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/cr.2011.13","volume":"21","author":"MS Hayden","year":"2011","unstructured":"Hayden MS, Ghosh S (2011) NF-\u03baB in immunobiology. Cell Res 21:223\u2013244. https:\/\/doi.org\/10.1038\/cr.2011.13","journal-title":"Cell Res"},{"key":"1786_CR15","doi-asserted-by":"publisher","first-page":"a000158","DOI":"10.1101\/cshperspect.a000158","volume":"2","author":"A Israel","year":"2010","unstructured":"Israel A (2010) The IKK complex, a central regulator of NF- B activation. Cold Spring Harb Perspect Biol 2:a000158\u2013a000158. https:\/\/doi.org\/10.1101\/cshperspect.a000158","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"1786_CR16","doi-asserted-by":"publisher","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","volume":"47","author":"S Kim","year":"2019","unstructured":"Kim S, Chen J, Cheng T et al (2019) PubChem 2019 update: improved access to chemical data. Nucleic Acids Res 47:D1102\u2013D1109. https:\/\/doi.org\/10.1093\/nar\/gky1033","journal-title":"Nucleic Acids Res"},{"key":"1786_CR17","doi-asserted-by":"publisher","first-page":"E453","DOI":"10.1152\/ajpendo.00204.2007","volume":"293","author":"CH Lang","year":"2007","unstructured":"Lang CH, Frost RA, Vary TC (2007) Regulation of muscle protein synthesis during sepsis and inflammation. Am J Physiol-Endocrinol Metabol 293:E453\u2013E459. https:\/\/doi.org\/10.1152\/ajpendo.00204.2007","journal-title":"Am J Physiol-Endocrinol Metabol"},{"key":"1786_CR18","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1107\/S0021889892009944","volume":"26","author":"RA Laskowski","year":"1993","unstructured":"Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283\u2013291. https:\/\/doi.org\/10.1107\/S0021889892009944","journal-title":"J Appl Crystallogr"},{"key":"1786_CR19","doi-asserted-by":"publisher","first-page":"e0195577","DOI":"10.1371\/journal.pone.0195577","volume":"13","author":"H-A Lee","year":"2018","unstructured":"Lee H-A, Hyun S-A, Byun B et al (2018) Electrophysiological mechanisms of vandetanib-induced cardiotoxicity: comparison of action potentials in rabbit purkinje fibers and pluripotent stem cell-derived cardiomyocytes. PLoS ONE 13:e0195577. https:\/\/doi.org\/10.1371\/journal.pone.0195577","journal-title":"PLoS ONE"},{"key":"1786_CR20","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","volume":"2","author":"T Liu","year":"2017","unstructured":"Liu T, Zhang L, Joo D, Sun S-C (2017) NF-\u03baB signaling in inflammation. Sign Transduct Target Ther 2:17023. https:\/\/doi.org\/10.1038\/sigtrans.2017.23","journal-title":"Sign Transduct Target Ther"},{"key":"1786_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.966463","author":"J Maly","year":"2022","unstructured":"Maly J, Emigh AM, DeMarco KR et al (2022) Structural modeling of the hERG potassium channel and associated drug interactions. Front Pharmacol. https:\/\/doi.org\/10.3389\/fphar.2022.966463","journal-title":"Front Pharmacol"},{"key":"1786_CR22","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.bbrc.2006.10.039","volume":"351","author":"JT Milnes","year":"2006","unstructured":"Milnes JT, Witchel HJ, Leaney JL et al (2006) hERG K+ channel blockade by the antipsychotic drug thioridazine: an obligatory role for the S6 helix residue F656. Biochem Biophys Res Commun 351:273\u2013280. https:\/\/doi.org\/10.1016\/j.bbrc.2006.10.039","journal-title":"Biochem Biophys Res Commun"},{"key":"1786_CR23","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.trci.2017.10.005","volume":"3","author":"RC Mohs","year":"2017","unstructured":"Mohs RC, Greig NH (2017) Drug discovery and development: role of basic biological research. Alzheimer\u2019s & Dementia: Transl Res Clin Interv 3:651\u2013657. https:\/\/doi.org\/10.1016\/j.trci.2017.10.005","journal-title":"Alzheimer\u2019s & Dementia: Transl Res Clin Interv"},{"key":"1786_CR24","doi-asserted-by":"publisher","first-page":"7822","DOI":"10.1021\/acs.jpcb.4c02662","volume":"128","author":"M Nemchinova","year":"2024","unstructured":"Nemchinova M, Schuurman-Wolters GK, Whittaker JJ et al (2024) exploring the ligand binding and conformational dynamics of the substrate-binding domain 1 of the ABC transporter GlnPQ. J Phys Chem B 128:7822\u20137832. https:\/\/doi.org\/10.1021\/acs.jpcb.4c02662","journal-title":"J Phys Chem B"},{"key":"1786_CR25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle NM, Banck M, James CA et al (2011) Open Babel: An open chemical toolbox. J Cheminform 3:33. https:\/\/doi.org\/10.1186\/1758-2946-3-33","journal-title":"J Cheminform"},{"key":"1786_CR26","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1124\/mol.105.016741","volume":"69","author":"M Perry","year":"2006","unstructured":"Perry M, Stansfeld PJ, Leaney J et al (2006) Drug binding interactions in the inner cavity of hERG channels: molecular insights from structure-activity relationships of clofilium and ibutilide analogs. Mol Pharmacol 69:509\u2013519. https:\/\/doi.org\/10.1124\/mol.105.016741","journal-title":"Mol Pharmacol"},{"key":"1786_CR27","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera\u2014a visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084","journal-title":"J Comput Chem"},{"key":"1786_CR28","doi-asserted-by":"publisher","first-page":"i109","DOI":"10.1136\/ard.2010.140533","volume":"70","author":"HB Schonthaler","year":"2011","unstructured":"Schonthaler HB, Guinea-Viniegra J, Wagner EF (2011) Targeting inflammation by modulating the Jun\/AP-1 pathway. Ann Rheum Dis 70:i109\u2013i112. https:\/\/doi.org\/10.1136\/ard.2010.140533","journal-title":"Ann Rheum Dis"},{"key":"1786_CR29","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1021\/ct900587b","volume":"6","author":"D Shivakumar","year":"2010","unstructured":"Shivakumar D, Williams J, Wu Y et al (2010) Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field. J Chem Theory Comput 6:1509\u20131519. https:\/\/doi.org\/10.1021\/ct900587b","journal-title":"J Chem Theory Comput"},{"key":"1786_CR30","doi-asserted-by":"publisher","unstructured":"Stevens-Sostre, W. A., Flores-Aldama, L., Bustos, D., Li, J., Morais-Cabral, J. H., Delemotte, L., & Robertson, G. A. (2024). An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation. Biophysical journal, 123(14), 2024\u20132037. https:\/\/doi.org\/10.1016\/j.bpj.2024.01.010","DOI":"10.1016\/j.bpj.2024.01.010"},{"key":"1786_CR31","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1016\/j.apsb.2022.02.002","volume":"12","author":"D Sun","year":"2022","unstructured":"Sun D, Gao W, Hu H, Zhou S (2022) Why 90% of clinical drug development fails and how to improve it? Acta Pharm Sin B 12:3049\u20133062. https:\/\/doi.org\/10.1016\/j.apsb.2022.02.002","journal-title":"Acta Pharm Sin B"},{"key":"1786_CR32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.2174\/156652309788488569","volume":"9","author":"S Tas","year":"2009","unstructured":"Tas S, Vervoordeldonk M, Tak P (2009) Gene therapy targeting nuclear factor-\u03baB: towards clinical application in inflammatory diseases and cancer. Curr Gene Ther 9:160\u2013170. https:\/\/doi.org\/10.2174\/156652309788488569","journal-title":"Curr Gene Ther"},{"key":"1786_CR33","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ (2010) AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334","journal-title":"J Comput Chem"},{"key":"1786_CR34","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.tips.2017.06.004","volume":"38","author":"JI Vandenberg","year":"2017","unstructured":"Vandenberg JI, Perozo E, Allen TW (2017) Towards a structural view of drug binding to hERG K + channels. Trends Pharmacol Sci 38:899\u2013907. https:\/\/doi.org\/10.1016\/j.tips.2017.06.004","journal-title":"Trends Pharmacol Sci"},{"key":"1786_CR35","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.cell.2017.03.048","volume":"169","author":"W Wang","year":"2017","unstructured":"Wang W, MacKinnon R (2017) Cryo-EM structure of the open human ether-\u00e0-go-go -related K + channel hERG. Cell 169:422-430.e10. https:\/\/doi.org\/10.1016\/j.cell.2017.03.048","journal-title":"Cell"},{"key":"1786_CR36","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse A, Bertoni M, Bienert S et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296\u2013W303. https:\/\/doi.org\/10.1093\/nar\/gky427","journal-title":"Nucleic Acids Res"},{"key":"1786_CR37","doi-asserted-by":"publisher","first-page":"31123","DOI":"10.1074\/jbc.274.44.31123","volume":"274","author":"Z Zhou","year":"1999","unstructured":"Zhou Z, Gong Q, January CT (1999) Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. J Biol Chem 274:31123\u201331126. https:\/\/doi.org\/10.1074\/jbc.274.44.31123","journal-title":"J Biol Chem"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01786-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-025-01786-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-025-01786-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:05:53Z","timestamp":1749719153000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-025-01786-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":37,"alternative-id":["1786"],"URL":"https:\/\/doi.org\/10.1007\/s10787-025-01786-y","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"assertion":[{"value":"25 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 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 that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}