{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:52:12Z","timestamp":1773946332903,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2024,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In the search of novel series of CFTR modulators, a library of mono and diacyl thioureas were prepared by sequential synthesis. When tested alone, the obtained compounds <jats:bold>5<\/jats:bold> and <jats:bold>6<\/jats:bold> poorly affected F508del\u2010CFTR conductance but, in combination with Lumacaftor, selected derivatives showed the ability to increase the activity of the approved modulator. Analogue <jats:bold>6\u2009i<\/jats:bold> displayed the most marked enhancing effect and acylthioureas <jats:bold>6\u2009d<\/jats:bold> and <jats:bold>6\u2009f<\/jats:bold> were also able to improve efficacy of Lumacaftor. All compounds proved to be non\u2010cytotoxic against different cancer cell lines. Good pharmacokinetic properties were predicted for derivatives <jats:bold>5<\/jats:bold> and <jats:bold>6<\/jats:bold>, thus supporting the value of these compounds for the development of novel modulators potentially useful for cystic fibrosis.<\/jats:p>","DOI":"10.1002\/cmdc.202300391","type":"journal-article","created":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T22:13:45Z","timestamp":1702851225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cyclic diacyl thioureas enhance activity of corrector Lumacaftor on F508del\u2010CFTR"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-7146","authenticated-orcid":false,"given":"Andrea","family":"Spallarossa","sequence":"first","affiliation":[{"name":"Department of Pharmacy Universit\u00e0 degli Studi di Genova  Viale Benedetto XV 3 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica IRCCS Istituto Giannina Gaslini  Via Gerolamo Gaslini, 5 16147 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Pesce","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica IRCCS Istituto Giannina Gaslini  Via Gerolamo Gaslini, 5 16147 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Millo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Biochemistry Universit\u00e0 degli Studi di Genova  Viale Benedetto XV 1 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Cichero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Universit\u00e0 degli Studi di Genova  Viale Benedetto XV 3 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camillo","family":"Rosano","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Unit IRCCS Ospedale Policlinico San Martino  Largo R. Benzi, 10 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-7891","authenticated-orcid":false,"given":"Matteo","family":"Lusardi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Universit\u00e0 degli Studi di Genova  Viale Benedetto XV 3 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Iervasi","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Unit IRCCS Ospedale Policlinico San Martino  Largo R. Benzi, 10 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Ponassi","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Unit IRCCS Ospedale Policlinico San Martino  Largo R. Benzi, 10 16132 Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00196314"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13619"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199502233320803"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djs481"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30337-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00576-6"},{"key":"e_1_2_8_7_1","unstructured":"The Clinical and Functional Translation of CFTR (CFTR2).https:\/\/www.cftr2.org\/."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15155"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32542-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20212006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-6-461"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2022.102239"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.05.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105185"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904709106"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25627"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201708-668PS"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102946"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA01781D"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.132207"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2020.152366"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.073056"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja507551z"},{"key":"e_1_2_8_24_1","author":"Scarsi A.","year":"2022","journal-title":"Mol. Diversity"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570260147"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2008.06.010"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520614666140407123526"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200700139"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19991216)38:24<3743::AID-ANIE3743>3.0.CO;2-U"},{"key":"e_1_2_8_31_1","unstructured":"R. Leardi C. Melzi G. Polotti CAT (Chemometric Agile Tool)http:\/\/gruppochemiometria.it\/index.php\/software."}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202300391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T09:38:33Z","timestamp":1760261913000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202300391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,2,16]]}},"alternative-id":["10.1002\/cmdc.202300391"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202300391","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]},"assertion":[{"value":"2023-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202300391"}}