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Pharm. Res."],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Raf kinase enzymes are often dysregulated in melanoma. While sorafenib demonstrates strong activity against wild-type B-Raf, it fails to effectively inhibit the mutated form of B-Raf. In this study, sorafenib served as a lead compound for the development of new derivatives designed to enhance inhibitory activity across multiple Raf isoforms (pan-Raf inhibitors). Novel naphthalene-based diarylamide derivatives were subsequently designed, synthesized, and evaluated for their biological activity against various Raf kinase isoforms and the melanoma A375 cell line. Among these, compound\n                    <jats:bold>9a<\/jats:bold>\n                    , containing a difluoromethoxy group, demonstrated strong inhibitory activity across B-Raf\n                    <jats:sup>WT<\/jats:sup>\n                    , B-Raf\n                    <jats:sup>V600E<\/jats:sup>\n                    , and c-Raf. Additionally, it induced G2\/M phase arrest and triggered dose-dependent apoptosis, effectively suppressing both cell proliferation and survival. Compound\n                    <jats:bold>9a<\/jats:bold>\n                    also exhibited high selectivity for Raf isoforms with minimal off-target effects, underscoring its specificity and therapeutic potential for Raf-driven malignancies.\n                  <\/jats:p>","DOI":"10.1007\/s12272-025-01533-5","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T22:30:21Z","timestamp":1738967421000},"page":"150-165","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening"],"prefix":"10.1007","volume":"48","author":[{"given":"Ahmed","family":"Elkamhawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama M.","family":"Ammar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anam Rana","family":"Gul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Jung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5455-9956","authenticated-orcid":false,"given":"Kyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"1533_CR1","doi-asserted-by":"publisher","first-page":"6877","DOI":"10.1021\/acs.jmedchem.1c00230","volume":"64","author":"MS Abdel-Maksoud","year":"2021","unstructured":"Abdel-Maksoud MS, El-Gamal MI, Lee BS, Gamal El-Din MM, Jeon HR, Kwon D, Ammar UM, Mersal KI, Ali EM, Lee K-T (2021) Discovery of new imidazo [2, 1-b] thiazole derivatives as potent pan-RAF inhibitors with promising in vitro and in vivo anti-melanoma activity. 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