{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:48:37Z","timestamp":1779306517403,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000947","name":"Australian Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>In silico<\/jats:italic> approaches identified <jats:bold>1<\/jats:bold>, <jats:italic>N<\/jats:italic>\u2010(6\u2010((4\u2010bromo\u2010 benzyl)amino)hexyl)\u20103,5\u2010bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2\u2010p53 protein\u2010protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97\u2005\u03bcM cell growth inhibitor of the MiaPaCa\u20102 pancreatic cell line. This is in keeping with our hypothesis that inhibiting this interaction would have an anti\u2010pancreatic cancer effect with S100A2, the validated PC drug target. A combination of focused library synthesis (three libraries, 24 compounds total) and cytotoxicity screening identified a propyl alkyl diamine spacer as optimal; the nature of the terminal phenyl substituent had limited impact on observed cytotoxicity, whereas <jats:italic>N<\/jats:italic>\u2010methylation was detrimental to activity. In total 15 human cancer cell lines were examined, with most analogues showing broad\u2010spectrum activity. Near uniform activity was observed against a panel of six pancreatic cancer cell lines: MiaPaCa\u20102, BxPC\u20103, AsPC\u20101, Capan\u20102, HPAC and PANC\u20101. In all cases there was good to excellent correlation between the predicted docking pose in the S100A2\u2010p53 binding groove and the observed cytotoxicity, especially in the pancreatic cancer cell line with high endogenous S100A2 expression. This supports S100A2 as a pancreatic cancer drug target.<\/jats:p>","DOI":"10.1002\/cmdc.202000949","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T22:17:07Z","timestamp":1622153827000},"page":"2851-2863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting the S100A2\u2010p53 Interaction with a Series of 3,5\u2010<i>Bis<\/i>(trifluoromethyl)benzene Sulfonamides: Synthesis and Cytotoxicity"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-9396","authenticated-orcid":false,"given":"Jufeng","family":"Sun","sequence":"first","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"},{"name":"Medicinal Chemistry School of Pharmacy Binzhou Medical University  Yantai 264003 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joey I.","family":"Ambrus","sequence":"additional","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia C.","family":"Russell","sequence":"additional","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-301X","authenticated-orcid":false,"given":"Jennifer R.","family":"Baker","sequence":"additional","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-5710","authenticated-orcid":false,"given":"Peter J.","family":"Cossar","sequence":"additional","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-7818","authenticated-orcid":false,"given":"Melanie J.","family":"Pirinen","sequence":"additional","affiliation":[{"name":"School of Environmental &amp; Life Sciences The University of Newcastle  Ourimbah NSW 2258 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-5792","authenticated-orcid":false,"given":"Jennette A.","family":"Sakoff","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics Group, Department of Medical Oncology Calvary Mater Newcastle Hospital  Edith Street Waratah NSW 2298 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4140-7785","authenticated-orcid":false,"given":"Christopher J.","family":"Scarlett","sequence":"additional","affiliation":[{"name":"School of Environmental &amp; Life Sciences The University of Newcastle  Ourimbah NSW 2258 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-863X","authenticated-orcid":false,"given":"Adam","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Chemistry School of Environmental &amp; Life Sciences The University of Newcastle University Drive  Callaghan NSW 2308 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0050"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0155"},{"key":"e_1_2_7_3_1","unstructured":"https:\/\/www.canceraustralia.gov.au\/publications-and-resources\/cancer-australia-publications\/pancreatic-cancer-fact-sheet. 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