{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T02:42:43Z","timestamp":1784428963313,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health (Ricerca Corrente)"},{"name":"\u201cPi\u00f9 unici che rari\u201d OdV"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous melanoma is the most dangerous and deadly form of human skin malignancy. Despite its rarity, it accounts for a staggering 80% of deaths attributed to cutaneous cancers overall. Moreover, its final stages often exhibit resistance to drug treatments, resulting in unfavorable outcomes. Hence, ensuring access to novel and improved chemotherapeutic agents is imperative for patients grappling with this severe ailment. Pyrazole and its fused systems derived thereof are heteroaromatic moieties widely employed in medicinal chemistry to develop effective drugs for various therapeutic areas, including inflammation, pain, oxidation, pathogens, depression, and fever. In a previous study, we described the biochemical properties of a newly synthesized group of imidazo\u2013pyrazole compounds. In this paper, to improve our knowledge of the pharmacological properties of these molecules, we conduct a differential proteomic analysis on a human melanoma cell line treated with one of these imidazo\u2013pyrazole derivatives. Our results detail the changes to the SKMEL-28 cell line proteome induced by 24, 48, and 72 h of 3e imidazo\u2013pyrazole treatment. Notably, we highlight the down-regulation of the Ras-responsive element binding protein 1 (RREB1), a member of the zinc finger transcription factors family involved in the tumorigenesis of melanoma. RREB1 is a downstream element of the MAPK pathway, and its activation is mediated by ERK1\/2 through phosphorylation.<\/jats:p>","DOI":"10.3390\/ijms25126760","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T03:46:29Z","timestamp":1718855189000},"page":"6760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Proteomics Approach Identifies RREB1 as a Crucial Molecular Target of Imidazo\u2013Pyrazole Treatment in SKMEL-28 Melanoma Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-3373","authenticated-orcid":false,"given":"Erika","family":"Iervasi","sequence":"first","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-706X","authenticated-orcid":false,"given":"Gabriela","family":"Coronel Vargas","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Bachetti","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kateryna","family":"Tkachenko","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-7146","authenticated-orcid":false,"given":"Andrea","family":"Spallarossa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7726","authenticated-orcid":false,"given":"Chiara","family":"Brullo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2949-9215","authenticated-orcid":false,"given":"Camillo","family":"Rosano","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-9761","authenticated-orcid":false,"given":"Sonia","family":"Carta","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Nuclear Medicine Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-9290","authenticated-orcid":false,"given":"Paola","family":"Barboro","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-3021","authenticated-orcid":false,"given":"Aldo","family":"Profumo","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-2458","authenticated-orcid":false,"given":"Marco","family":"Ponassi","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/cber.188301602194","article-title":"Einwirkung von Acetessigester auf Phenylhydrazin","volume":"16","author":"Knorr","year":"1883","journal-title":"Berichte Dtsch. Chem. 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