{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:00:18Z","timestamp":1793797218499,"version":"4.6.1"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.ejmech.2022.115011","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T12:45:54Z","timestamp":1670330754000},"page":"115011","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Design, synthesis, biological evaluation and crystal structure determination of dual modulators of carbonic anhydrases and estrogen receptors"],"prefix":"10.1016","volume":"246","author":[{"given":"Annachiara","family":"Tinivella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome C.","family":"Nwachukwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Angeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Laura","family":"Benatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Pinzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Izard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ferraroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rangarajan","family":"Erumbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Christodoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Passarella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall W.","family":"Nettles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2474-0607","authenticated-orcid":false,"given":"Giulio","family":"Rastelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2022.115011_bib1","doi-asserted-by":"crossref","first-page":"7874","DOI":"10.1021\/jm5006463","article-title":"Polypharmacology: challenges and opportunities in drug discovery","volume":"57","author":"Anighoro","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib2","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1080\/14756366.2021.1945049","article-title":"Multitargeting approaches involving carbonic anhydrase inhibitors: hybrid drugs against a variety of disorders","volume":"36","author":"Supuran","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/cmdc.201600474","article-title":"Probing an allosteric pocket of CDK2 with small molecules","volume":"12","author":"Christodoulou","year":"2017","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2022.115011_bib4","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib6","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkr777","article-title":"ChEMBL: a large-scale bioactivity database for drug discovery","volume":"40","author":"Gaulton","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib7","doi-asserted-by":"crossref","first-page":"D1083","DOI":"10.1093\/nar\/gkt1031","article-title":"The ChEMBL bioactivity database: an update","volume":"42","author":"Bento","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib8","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkw1074","article-title":"The ChEMBL database in 2017","volume":"45","author":"Gaulton","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/med.10025","article-title":"Carbonic anhydrase inhibitors","volume":"23","author":"Supuran","year":"2003","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2022.115011_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(96)00198-2","article-title":"Structure and mechanism of carbonic anhydrase","volume":"74","author":"Lindskog","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.ejmech.2022.115011_bib11","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1021\/cr200176r","article-title":"Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms?","volume":"112","author":"Alterio","year":"2012","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2022.115011_bib12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nm1534","article-title":"Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation","volume":"13","author":"Gao","year":"2007","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejmech.2022.115011_bib13","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1023\/A:1002143802926","article-title":"The role of carbonic anhydrase inhibitors in the management of macular edema","volume":"97","author":"Wolfensberger","year":"1999","journal-title":"Doc. Ophthalmol."},{"key":"10.1016\/j.ejmech.2022.115011_bib14","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2174\/156802607780636726","article-title":"Carbonic anhydrase inhibitors as anticonvulsant agents","volume":"7","author":"Thiry","year":"2007","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib15","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1021\/jm300031j","article-title":"Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo","volume":"55","author":"Carta","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib16","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2174\/138161208783877947","article-title":"Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides","volume":"14","author":"Supuran","year":"2008","journal-title":"Curr. Pharmaceut. Des."},{"key":"10.1016\/j.ejmech.2022.115011_bib17","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1021\/jm031116j","article-title":"Carbonic anhydrase inhibitors: synthesis and topical intraocular pressure lowering effects of fluorine-containing inhibitors devoid of enhanced reactivity","volume":"47","author":"de Leval","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib18","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1158\/0008-5472.CAN-08-2470","article-title":"Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH","volume":"69","author":"Chiche","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib19","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.bbapap.2009.07.027","article-title":"Carbonic anhydrase IX: biochemical and crystallographic characterization of a novel antitumor target","author":"De Simone","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2022.115011_bib20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/COC.0000000000000691","article-title":"A phase 1 study of SLC-0111, a novel inhibitor of carbonic anhydrase IX, in patients with advanced solid tumors","volume":"43","author":"McDonald","year":"2020","journal-title":"Am. J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2022.115011_bib21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10555-019-09799-0","article-title":"The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond","volume":"38","author":"Pastorekova","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"10.1016\/j.ejmech.2022.115011_bib22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13000-016-0495-1","article-title":"Carbonic anhydrase IX is a marker of hypoxia and correlates with higher Gleason scores and ISUP grading in prostate cancer","volume":"11","author":"Ambrosio","year":"2016","journal-title":"Diagn. Pathol."},{"key":"10.1016\/j.ejmech.2022.115011_bib23","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/14756366.2018.1538980","article-title":"Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity","volume":"34","author":"Logozzi","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib24","doi-asserted-by":"crossref","first-page":"14212","DOI":"10.1073\/pnas.97.26.14212","article-title":"Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers","volume":"97","author":"Ulmasov","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejmech.2022.115011_bib25","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1080\/13543776.2018.1508453","article-title":"Carbonic anhydrase inhibitors as antitumor\/antimetastatic agents: a patent review (2008-2018)","volume":"28","author":"Nocentini","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"key":"10.1016\/j.ejmech.2022.115011_bib26","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14143297","article-title":"Cancer therapeutic targeting of hypoxia induced carbonic anhydrase IX: from bench to bedside","volume":"14","author":"McDonald","year":"2022","journal-title":"Cancers"},{"key":"10.1016\/j.ejmech.2022.115011_bib27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.critrevonc.2004.02.001","article-title":"Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion","volume":"51","author":"Platet","year":"2004","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"10.1016\/j.ejmech.2022.115011_bib28","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.bioorg.2017.02.011","article-title":"Estrogen receptor agonists\/antagonists in breast cancer therapy: a critical review","volume":"71","author":"Jameera Begam","year":"2017","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib29","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.steroids.2008.04.006","article-title":"ERbeta in breast cancer--onlooker, passive player, or active protector?","volume":"73","author":"Fox","year":"2008","journal-title":"Steroids"},{"key":"10.1016\/j.ejmech.2022.115011_bib30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1158\/0008-5472.CAN-03-2446","article-title":"Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest","volume":"64","author":"Paruthiyil","year":"2004","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib31","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/925703","article-title":"Biologic roles of estrogen receptor-\u03b2 and insulin-like growth factor-2 in triple-negative breast cancer","volume":"2015","author":"Hamilton","year":"2015","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.ejmech.2022.115011_bib32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jnci\/djw236","article-title":"Estrogen receptor \u03b2 as a therapeutic target in breast cancer stem cells","volume":"109","author":"Ma","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.ejmech.2022.115011_bib33","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.3892\/ol.2017.6314","article-title":"ER\u03b1 and ER\u03b2 co-expression: an indicator of aggressive tumors and hormonal sensitivity","volume":"14","author":"Oueslati","year":"2017","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.ejmech.2022.115011_bib34","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1038\/ncomms6383","article-title":"The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer","volume":"5","author":"Chakravarty","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2022.115011_bib35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fonc.2018.00002","article-title":"Estrogens and their receptors in prostate cancer: therapeutic implications","volume":"8","author":"Di Zazzo","year":"2018","journal-title":"Front. Oncol."},{"key":"10.1016\/j.ejmech.2022.115011_bib36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gene.2017.04.027","article-title":"Carbonic anhydrase XII functions in health and disease","volume":"623","author":"Waheed","year":"2017","journal-title":"Gene"},{"key":"10.1016\/j.ejmech.2022.115011_bib37","doi-asserted-by":"crossref","first-page":"8720","DOI":"10.1158\/1078-0432.CCR-04-1235","article-title":"Intermittent hypoxia induces proteasome-dependent down-regulation of estrogen receptor alpha in human breast carcinoma","volume":"10","author":"Cooper","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib38","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1158\/0008-5472.CAN-07-6151","article-title":"Estrogen receptor regulation of carbonic anhydrase XII through a distal enhancer in breast cancer","volume":"68","author":"Barnett","year":"2008","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib39","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1677\/erc.1.01216","article-title":"Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin\/tamoxifen therapy for breast cancer","volume":"13","author":"Generali","year":"2006","journal-title":"Endocr. Relat. Cancer"},{"key":"10.1016\/j.ejmech.2022.115011_bib40","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1349-7006.2001.tb01064.x","article-title":"Hypoxia reduces hormone responsiveness of human breast cancer cells","volume":"92","author":"Kurebayashi","year":"2001","journal-title":"Jpn. J. Cancer Res."},{"key":"10.1016\/j.ejmech.2022.115011_bib42","doi-asserted-by":"crossref","first-page":"5544","DOI":"10.1021\/jm060531j","article-title":"Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX","volume":"49","author":"De Simone","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib43","unstructured":"https:\/\/www.ebi.ac.uk\/chembl\/compound_report_card\/CHEMBL386049\/."},{"key":"10.1016\/j.ejmech.2022.115011_bib44","unstructured":"https:\/\/www.drugbank.ca\/drugs\/DB07933."},{"key":"10.1016\/j.ejmech.2022.115011_bib45","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1021\/jm060491j","article-title":"Benzopyrans are selective estrogen receptor \u03b2 agonists with novel activity in models of benign prostatic hyperplasia","volume":"49","author":"Norman","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib46","unstructured":"https:\/\/www.ebi.ac.uk\/chembl\/compound_report_card\/CHEMBL278703\/."},{"key":"10.1016\/j.ejmech.2022.115011_bib47","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1002\/cmdc.201800687","article-title":"Structure-activity relationships of hexahydrocyclopenta[c]quinoline derivatives as allosteric inhibitors of CDK2 and EGFR","volume":"13","author":"Carlino","year":"2018","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2022.115011_bib48","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3109\/14756360009040713","article-title":"Carbonic anhydrase inhibitors: aromatic sulfonamides and disulfonamides act as efficient tumor growth inhibitors","volume":"15","author":"Supuran","year":"2000","journal-title":"J. Enzym. Inhib."},{"key":"10.1016\/j.ejmech.2022.115011_bib49","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1016\/j.bmcl.2007.04.051","article-title":"Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 2: structure-activity relationship studies on the benzopyran scaffold","volume":"17","author":"Richardson","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2022.115011_bib50","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/39645","article-title":"Molecular basis of agonism and antagonism in the oestrogen receptor","volume":"389","author":"Brzozowski","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2022.115011_bib51","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1002\/slct.201700531","article-title":"Combinatorial design of isoform-selective N-Alkylated benzimidazole-based inhibitors of carbonic anhydrases","volume":"2","author":"\u010capkauskait\u0117","year":"2017","journal-title":"ChemistrySelect"},{"key":"10.1016\/j.ejmech.2022.115011_bib52","doi-asserted-by":"crossref","first-page":"9004","DOI":"10.1021\/acs.jmedchem.5b01343","article-title":"Efficient expression and crystallization system of cancer-associated carbonic anhydrase isoform IX","volume":"58","author":"Leitans","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib53","doi-asserted-by":"crossref","first-page":"6776","DOI":"10.1021\/jm300818k","article-title":"Development of potent carbonic anhydrase inhibitors incorporating both sulfonamide and sulfamide groups","volume":"55","author":"D'Ambrosio","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib54","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ejmech.2018.11.073","article-title":"Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety","volume":"163","author":"Buemi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib55","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1021\/acs.jmedchem.7b00264","article-title":"Probing molecular interactions between human carbonic anhydrases (hCAs) and a novel class of benzenesulfonamides","volume":"60","author":"Bruno","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib56","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.urolonc.2005.11.005","article-title":"Development of the VCaP androgen-independent model of prostate cancer","volume":"24","author":"Loberg","year":"2006","journal-title":"Urol. Oncol."},{"key":"10.1016\/j.ejmech.2022.115011_bib57","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1038\/s41598-020-60844-3","article-title":"A systematic study of the impact of estrogens and selective estrogen receptor modulators on prostate cancer cell proliferation","volume":"10","author":"Lafront","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2022.115011_bib58","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1101\/gad.1446006","article-title":"A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer","volume":"20","author":"Eeckhoute","year":"2006","journal-title":"Genes Dev."},{"key":"10.1016\/j.ejmech.2022.115011_bib59","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mce.2007.07.006","article-title":"Estrogen receptor DNA binding is not required for estrogen-induced breast cell growth","volume":"277","author":"DeNardo","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.ejmech.2022.115011_bib60","doi-asserted-by":"crossref","first-page":"14930","DOI":"10.1073\/pnas.1203574109","article-title":"Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes","volume":"109","author":"Delfosse","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejmech.2022.115011_bib61","doi-asserted-by":"crossref","first-page":"864","DOI":"10.15252\/msb.20156701","article-title":"Predictive features of ligand-specific signaling through the estrogen receptor","volume":"12","author":"Nwachukwu","year":"2016","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.ejmech.2022.115011_bib62","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nchembio.1214","article-title":"Ligand-binding dynamics rewire cellular signaling via estrogen receptor-\u03b1","volume":"9","author":"Srinivasan","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2022.115011_bib63","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fphar.2015.00157","article-title":"Computational polypharmacology comes of age","volume":"6","author":"Rastelli","year":"2015","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.115011_bib64","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.ejmech.2017.10.021","article-title":"Dual or multi-targeting inhibitors: the next generation anticancer agents","volume":"143","author":"Raghavendra","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib65","series-title":"Schr\u00f6dinger Release 2018-3","year":"2018"},{"key":"10.1016\/j.ejmech.2022.115011_bib66","series-title":"Schr\u00f6dinger Release 2018-3","year":"2018"},{"key":"10.1016\/j.ejmech.2022.115011_bib67","series-title":"OMEGA 3.0.1.2","year":"2018"},{"key":"10.1016\/j.ejmech.2022.115011_bib68","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1021\/ci100031x","article-title":"Conformer generation with OMEGA: algorithm and validation using high quality structures from the protein databank and cambridge structural database","volume":"50","author":"Hawkins","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2022.115011_bib69","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.ygeno.2019.06.021","article-title":"Drug databases and their contributions to drug repurposing","volume":"112","author":"Masoudi-Sobhanzadeh","year":"2020","journal-title":"Genomics"},{"key":"10.1016\/j.ejmech.2022.115011_bib70","first-page":"1656","article-title":"Exploration of databases and methods supporting drug repurposing: a comprehensive survey, Brief","volume":"22","author":"Tanoli","year":"2021","journal-title":"Bioinf"},{"key":"10.1016\/j.ejmech.2022.115011_bib71","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.2174\/1568026619666181129142127","article-title":"Internet resources for drug discovery and design","volume":"18","author":"Potemkin","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib72","series-title":"ROCS 3.2.2.2","year":"2018"},{"key":"10.1016\/j.ejmech.2022.115011_bib73","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1021\/jm0603365","article-title":"Comparison of shape-matching and docking as virtual screening tools","volume":"50","author":"Hawkins","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib74","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1021\/jm900818s","article-title":"Molecular shape and medicinal chemistry: a perspective","volume":"53","author":"Nicholls","year":"2010","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib75","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0018845","article-title":"Systematic exploitation of multiple receptor conformations for virtual ligand screening","volume":"6","author":"Bottegoni","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2022.115011_bib76","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10822-008-9168-9","article-title":"Multiple protein structures and multiple ligands: effects on the apparent goodness of virtual screening results","volume":"22","author":"Sheridan","year":"2008","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2022.115011_bib77","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1016\/j.drudis.2018.08.007","article-title":"Selection of protein conformations for structure-based polypharmacology studies","volume":"23","author":"Pinzi","year":"2018","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2022.115011_bib78","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1021\/ci5001604","article-title":"Best of both worlds: on the complementarity of ligand-based and structure-based virtual screening","volume":"54","author":"Broccatelli","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2022.115011_bib79","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1152\/physrev.2001.81.4.1535","article-title":"Mechanisms of estrogen action","volume":"81","author":"Nilsson","year":"2001","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejmech.2022.115011_bib80","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1021\/ci8002254","article-title":"Protein\u2212Ligand docking against non-native protein conformers","volume":"48","author":"Verdonk","year":"2008","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2022.115011_bib81","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20184331","article-title":"Molecular docking: shifting paradigms in drug discovery","volume":"20","author":"Pinzi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2022.115011_bib82","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2022.115011_bib83","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"10.1016\/j.ejmech.2022.115011_bib84","series-title":"Biochemistry","first-page":"45","article-title":"Carbonic anhydrase: an insight into the zinc binding site and into the active cavity through metal substitution","author":"Bertini","year":"1982"},{"key":"10.1016\/j.ejmech.2022.115011_bib85","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib86","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib87","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision Glide: docking and scoring incorporating a model of hydrophobic enclosure for Protein\u2212Ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib88","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: a force field providing broad coverage of drug-like small molecules and proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.ejmech.2022.115011_bib89","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced Fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib90","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/S0021-9258(18)62326-9","article-title":"The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C","volume":"246","author":"Khalifah","year":"1971","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib91","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1021\/jm300529u","article-title":"Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts","volume":"55","author":"Gieling","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib92","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0223-5234(99)80039-7","article-title":"Carbonic anhydrase inhibitors \u2013 Part 57: quantum chemical QSAR of a group of 1,3,4-thiadiazole- and 1,3,4-thiadiazoline disulfonamides with carbonic anhydrase inhibitory properties","volume":"34","author":"Supuran","year":"1999","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib93","doi-asserted-by":"crossref","DOI":"10.1002\/0471142727.mb1508s73","article-title":"High-throughput real-time quantitative reverse transcription PCR","author":"Bookout","year":"2006","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"10.1016\/j.ejmech.2022.115011_bib94","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1107\/S0907444909047374","article-title":"Integration, scaling, space-group assignment and post-refinement","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Crystallogr. D"},{"key":"10.1016\/j.ejmech.2022.115011_bib95","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1107\/S0907444911001314","article-title":"REFMAC5 for the refinement of macromolecular crystal structures","volume":"67","author":"Murshudov","year":"2011","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2022.115011_bib96","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1107\/S090744491200251X","article-title":"JLigand: a graphical tool for the CCP4 template-restraint library","volume":"68","author":"Lebedev","year":"2012","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2022.115011_bib97","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2022.115011_bib98","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2022.115011_bib99","series-title":"International Tables for Crystallography","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1107\/97809553602060000862","article-title":"ARP\/wARP \u2013 automated model building and refinement","author":"Lamzin","year":"2012"},{"key":"10.1016\/j.ejmech.2022.115011_bib100","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejmech.2022.115011_bib101","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nchembio.451","article-title":"Coupling of receptor conformation and ligand orientation determine graded activity","volume":"6","author":"Bruning","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2022.115011_bib102","series-title":"Methods in Enzymology","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"[20] Processing of X-ray diffraction data collected in oscillation mode","author":"Otwinowski","year":"1997"},{"key":"10.1016\/j.ejmech.2022.115011_bib103","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ymeth.2011.07.005","article-title":"The Phenix software for automated determination of macromolecular structures","volume":"55","author":"Adams","year":"2011","journal-title":"Methods"},{"key":"10.1016\/j.ejmech.2022.115011_bib104","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nchembio.76","article-title":"NF\u03baB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses","volume":"4","author":"Nettles","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2022.115011_bib105","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S2052252514009324","article-title":"The PDB_REDO server for macromolecular structure model optimization","volume":"1","author":"Joosten","year":"2014","journal-title":"IUCrJ"},{"key":"10.1016\/j.ejmech.2022.115011_bib106","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1016\/j.str.2013.07.025","article-title":"Improved crystallographic structures using extensive combinatorial refinement","volume":"21","author":"Nwachukwu","year":"2013","journal-title":"Structure"},{"key":"10.1016\/j.ejmech.2022.115011_bib107","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1107\/S0907444911007281","article-title":"Presenting your structures: the CCP4mg molecular-graphics software","volume":"67","author":"McNicholas","year":"2011","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422009138?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422009138?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:50:24Z","timestamp":1759330224000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523422009138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":106,"alternative-id":["S0223523422009138"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.115011","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis, biological evaluation and crystal structure determination of dual modulators of carbonic anhydrases and estrogen receptors","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.115011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"115011"}}