{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:01:00Z","timestamp":1762732860334,"version":"build-2065373602"},"reference-count":24,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","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":[[2025,11,6]]},"abstract":"<jats:p>\n                    Multiple myeloma is a rare blood cancer that develops from abnormal plasma cells in the bone marrow. Treatment of multiple myeloma remains an enormous challenge. In this work, hybrid compounds are developed and studied for their potential use against multiple myeloma. The compounds are designed to act by a dual mechanism of action, activation of the p53 pathway, and inhibition of the ataxia telangiectasia and Rad3\u2010related protein (ATR). To evaluate the selectivity for the p53 pathway, the compounds are first evaluated in an isogenic pair of HCT116 colon cancer cell lines, with and without p53, and in two breast cancer cell lines expressing different forms of p53. Then, the growth inhibitory effect of the hybrid compounds is tested against the multiple myeloma cell lines RPMI 8226 (mutant p53) and MM.1S (wild\u2010type p53). At the same time, compound\n                    <jats:bold>15<\/jats:bold>\n                    is confirmed to inhibit doxorubicin\u2010 but not UV\u2010induced DNA damage response via the ATR\/Chk1 signaling pathway. The hybrids show lower IC\n                    <jats:sub>50<\/jats:sub>\n                    values compared to the fragments alone, highlighting the potential for using hybrid molecules containing two pharmacophores with complementary activities. These results suggest that novel hybrid molecules may serve as new leads against multiple myeloma.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500600","type":"journal-article","created":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T13:29:16Z","timestamp":1757856556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hybrid Molecules of p53 Activators and Protoflavones to Target Multiple Myeloma"],"prefix":"10.1002","volume":"20","author":[{"given":"Francisca","family":"Lopes","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa  Av. Prof. Gama Pinto 1649\u2013003 Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"Girst","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  E\u00f6tv\u00f6s str. 6 H\u20106720 Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences University of Geneva  Rue Michel\u2010Servet 1 1211 Gen\u00e8ve 4 Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva  Rue Michel\u2010Servet 1 1211 Gen\u00e8ve 4 Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo J. F.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa  Av. 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Prof. Gama Pinto 1649\u2013003 Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE Faculty of Pharmacy University of Porto  Rua de Jorge Viterbo Ferreira 228 4050\u2013313 Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Natural Products Kaohsiung Medical University  Shih\u2010Chuan first Road. 100 Kaohsiung 807 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Cuendet","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences University of Geneva  Rue Michel\u2010Servet 1 1211 Gen\u00e8ve 4 Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva  Rue Michel\u2010Servet 1 1211 Gen\u00e8ve 4 Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-3472","authenticated-orcid":false,"given":"Attila","family":"Hunyadi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  E\u00f6tv\u00f6s str. 6 H\u20106720 Szeged Hungary"},{"name":"Graduate Institute of Natural Products Kaohsiung Medical University  Shih\u2010Chuan first Road. 100 Kaohsiung 807 Taiwan"},{"name":"HUN\u2010REN\u2010SZTE Biologically Active Natural Products Research Group  E\u00f6tv\u00f6s str. 6 H\u20106720 Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-9353","authenticated-orcid":false,"given":"Maria M. M.","family":"Santos","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa  Av. Prof. Gama Pinto 1649\u2013003 Lisboa Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13020217"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2016.11.004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00529-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27422"},{"key":"e_1_2_8_6_1","unstructured":"International Agency for Research on Cancer. Cancer Today (GLOBOCAN 2022 version 1.1). World Health Organization 2025. 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