{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:47:00Z","timestamp":1790272020754,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The X\u2010chromosome\u2010linked inhibitor of apoptosis protein (XIAP) plays a crucial role in controlling cell survival across multiple regulated cell death pathways and coordinating a range of inflammatory signalling events. The discovery of selective inhibitors for XIAP\u2010BIR2, able to disrupt the direct physical interaction between XIAP and RIPK2, offer promising therapeutic options for NOD2\u2010mediated diseases like Crohn's disease, sarcoidosis, and Blau syndrome. The objective of this study was to design, synthesize, and evaluate small synthetic molecules with binding selectivity to XIAP\u2010BIR2 domain. To achieve this, we applied an interdisciplinary drug design approach and firstly we have synthesized an initial fragment library to achieve a first XIAP inhibition activity. Then using a growing strategy, larger compounds were synthesized and one of them presents a good selectivity for XIAP\u2010BIR2 versus XIAP\u2010BIR3 domain, compound <jats:bold>20\u2009c<\/jats:bold>. The ability of compound <jats:bold>20\u2009c<\/jats:bold> to block the NOD1\/2 pathway was confirmed in cell models. These data show that we have synthesized molecules capable of blocking NOD1\/2 signalling pathways <jats:italic>in cellulo<\/jats:italic>, and ultimately leading to new anti\u2010inflammatory compounds.<\/jats:p>","DOI":"10.1002\/cmdc.202400567","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T06:35:27Z","timestamp":1728023727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Towards New Anti\u2010Inflammatory Agents: Design, Synthesis and Evaluation of Molecules Targeting XIAP\u2010BIR2"],"prefix":"10.1002","volume":"20","author":[{"given":"Marc","family":"Farag","sequence":"first","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4029-6777","authenticated-orcid":false,"given":"Nicolas","family":"Guedeney","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-1843","authenticated-orcid":false,"given":"Florian","family":"Schwalen","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymeric","family":"Zadoroznyj","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm) LNC UMR1231  Dijon France"},{"name":"Universit\u00e9 de Bourgogne Franche-Comt\u00e9 LNC UMR1231  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Barczyk","sequence":"additional","affiliation":[{"name":"Univ. Lille Inserm CHU Lille U1286 \u2013 INFINITE \u2013 Institute for Translational Research in Inflammation  F-59000 Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Giret","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Antraygues","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Wang","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Cornu","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Suzanne","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3984-5812","authenticated-orcid":false,"given":"Marc","family":"Since","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-2244","authenticated-orcid":false,"given":"Anne","family":"Sophie Voisin\u2010Chiret","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2181","authenticated-orcid":false,"given":"Laurence","family":"Dubrez","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (Inserm) LNC UMR1231  Dijon France"},{"name":"Universit\u00e9 de Bourgogne Franche-Comt\u00e9 LNC UMR1231  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Leleu\u2010Chavain","sequence":"additional","affiliation":[{"name":"Univ. Lille Inserm CHU Lille U1286 \u2013 INFINITE \u2013 Institute for Translational Research in Inflammation  F-59000 Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-1753","authenticated-orcid":false,"given":"Charline","family":"Kieffer","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Sopkova\u2010de Oliveira Santos","sequence":"additional","affiliation":[{"name":"Department Normandie Univ UNICAEN CERMN  bd Becquerel F-14000 Caen, Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.45"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065125"},{"key":"e_1_2_8_3_1","unstructured":"\u00a0"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/44617"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00274-4"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00544-X"},{"key":"e_1_2_8_7_1","unstructured":"\u00a0"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907131106"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303090"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.024"},{"key":"e_1_2_8_11_1","unstructured":"\u00a0"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.01.016"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899372"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25363"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.04.014"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","unstructured":"S. Jensen J.\u2005B. Seidelin E.\u2005C. LaCasse O.\u2005H. Nielsen Sci. Signaling2020 13 eaax8295.","DOI":"10.1126\/scisignal.aax8295"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444913016284"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01668"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.3993"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401826"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.04.096"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400732v"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","unstructured":"M. Lethier K. Huard M. Hons A. Favier B. Brutscher E. Boeri\u2005Erba D.\u2005W. Abbott S. Cusack E. Pellegrini Life Sci. Alliance2023 6 e202201784.","DOI":"10.26508\/lsa.202201784"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/35050012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20289"},{"key":"e_1_2_8_26_1","unstructured":"\u00a0"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.23354"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4067"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21367"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct5010406"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00935"},{"key":"e_1_2_8_32_1","unstructured":"\u00a0"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct200133y"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct100578z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19980730)19:10<1179::AID-JCC6>3.0.CO;2-J"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21287"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2015.1032936"},{"key":"e_1_2_8_39_1","unstructured":"\u00a0"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar000033j"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.1998.10508279"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","unstructured":"G. Wolber T. Langer J Chem Inf Model2005 45 160-169.","DOI":"10.1021\/ci049885e"},{"key":"e_1_2_8_43_1","unstructured":"BIOVIA Dassault Syst\u00e8mes Discovery Studio 2019 San Diego: Dassault Syst\u00e8mes 2019. ."},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21797"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr366"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.1012"},{"key":"e_1_2_8_47_1","unstructured":"\u00a0"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800382h"},{"key":"e_1_2_8_49_1","unstructured":"\u00a0"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.08.009"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.05.054"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00156-9"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00706"},{"key":"e_1_2_8_54_1","unstructured":"\u00a0"},{"key":"e_1_2_8_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201601361"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.02.086"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9600914"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/00304948.2016.1127096"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202400567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:41:45Z","timestamp":1760265705000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202400567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1,14]]}},"alternative-id":["10.1002\/cmdc.202400567"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202400567","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]},"assertion":[{"value":"2024-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202400567"}}