{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:57:59Z","timestamp":1790114279082,"version":"4.0.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["182716"],"award-info":[{"award-number":["182716"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","award":["F-11970"],"award-info":[{"award-number":["F-11970"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Bergen","award":["The Medical Student Research Programme at the Faculty of Medicine"],"award-info":[{"award-number":["The Medical Student Research Programme at the Faculty of Medicine"]}]},{"name":"University of Bergen","award":["The Medical Student research Programme at The Faculty of Medicine"],"award-info":[{"award-number":["The Medical Student research Programme at The Faculty of Medicine"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine\/threonine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Using <jats:italic>in vitro<\/jats:italic> cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with viability IC<jats:sub>50<\/jats:sub> doses in the range of 0.18\u20132.6 \u03bcM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two <jats:italic>B-Raf Proto-Oncogene<\/jats:italic> (BRAF) inhibitor resistant metastatic melanoma cell lines. Further <jats:italic>in vivo<\/jats:italic> studies should be performed to determine the treatment potential of CCT196969 in patients with treatment-na\u00efve and resistant melanoma brain metastasis.<\/jats:p>","DOI":"10.1371\/journal.pone.0273711","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T20:53:23Z","timestamp":1662756803000},"page":"e0273711","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Agathe","family":"Reigstad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Frantzen","family":"Herdlev\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Rigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuyen","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Vidhammer","family":"Bj\u00f8rnstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7557-3784","authenticated-orcid":true,"given":"Synn\u00f8ve Nymark","family":"Aasen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Preis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Haan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje","family":"Sundstr\u00f8m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-3703","authenticated-orcid":true,"given":"Frits","family":"Thorsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"issue":"2","key":"pone.0273711.ref001","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ejcsup.2013.07.012","article-title":"Melanoma epidemiology, biology and prognosis","volume":"11","author":"Z. 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