{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:10:08Z","timestamp":1762341008284,"version":"3.40.5"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100002628","name":"Incheon National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002628","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1016\/j.lfs.2017.06.021","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T12:46:56Z","timestamp":1498049216000},"page":"37-44","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Discovery of a novel pan-RAF inhibitor with potent anti-tumor activity in preclinical models of BRAF V600E mutant cancer"],"prefix":"10.1016","volume":"183","author":[{"given":"Sung Pyo","family":"Hong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-8116","authenticated-orcid":false,"given":"Soon Kil","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2017.06.021_bb0005","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1158\/0008-5472.CAN-03-3433","article-title":"V599EB-RAF is an oncogene in melanocytes","volume":"64","author":"Wellbrock","year":"2004","journal-title":"Cancer Res."},{"key":"10.1016\/j.lfs.2017.06.021_bb0010","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/nrc1503","article-title":"Targeting the mitogen-activated protein kinase cascade to treat cancer","volume":"4","author":"Sebolt-Leopold","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0015","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc969","article-title":"Targeting RAS signalling pathways in cancer therapy","volume":"3","author":"Downward","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0020","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1517\/14728222.2011.645805","article-title":"Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy","volume":"16","author":"Santarpia","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.lfs.2017.06.021_bb0025","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0898-6568(02)00139-0","article-title":"Mechanisms of regulating the Raf kinase family","volume":"15","author":"Chong","year":"2003","journal-title":"Cell. Signal."},{"key":"10.1016\/j.lfs.2017.06.021_bb0030","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nrm1498","article-title":"The RAF proteins take centre stage","volume":"5","author":"Wellbrock","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0035","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrm3979","article-title":"Regulation of RAF protein kinases in ERK signalling","volume":"16","author":"Lavoie","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0040","first-page":"3595","article-title":"Active Ras induces heterodimerization of cRaf and BRaf","volume":"61","author":"Weber","year":"2001","journal-title":"Cancer Res."},{"key":"10.1016\/j.lfs.2017.06.021_bb0045","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1128\/MCB.26.6.2262-2272.2006","article-title":"Regulation and role of Raf-1\/B-Raf heterodimerization","volume":"26","author":"Rushworth","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0050","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/carcin\/bgp337","article-title":"Targets of Raf in tumorigenesis","volume":"31","author":"Niault","year":"2010","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.lfs.2017.06.021_bb0055","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1200\/JCO.2010.32.4327","article-title":"Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma","volume":"29","author":"Long","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0060","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1002\/cncr.26724","article-title":"NRAS mutation status is an independent prognostic factor in metastatic melanoma","volume":"118","author":"Jakob","year":"2012","journal-title":"Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0065","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1756-8722-5-3","article-title":"Current management and novel agents for malignant melanoma","volume":"5","author":"Lee","year":"2012","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0070","doi-asserted-by":"crossref","first-page":"9719","DOI":"10.1158\/0008-5472.CAN-05-1683","article-title":"Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF","volume":"65","author":"Emuss","year":"2005","journal-title":"Cancer Res."},{"key":"10.1016\/j.lfs.2017.06.021_bb0075","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2017.06.021_bb0080","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.molcel.2005.10.022","article-title":"Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization","volume":"20","author":"Garnett","year":"2005","journal-title":"Mol. Cell"},{"key":"10.1016\/j.lfs.2017.06.021_bb0085","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cell.2009.12.040","article-title":"Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF","volume":"140","author":"MHeidorn","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.lfs.2017.06.021_bb0090","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1002011","article-title":"Inhibition of mutated, activated BRAF in metastatic melanoma","volume":"363","author":"Flaherty","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.lfs.2017.06.021_bb0095","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0140-6736(12)60398-5","article-title":"Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial","volume":"379","author":"Falchook","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.lfs.2017.06.021_bb0100","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1056\/NEJMoa1112302","article-title":"Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib","volume":"366","author":"Sosman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.lfs.2017.06.021_bb0105","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1038\/onc.2012.453","article-title":"NRAS mutant melanoma: biological behavior and future strategies for therapeutic management","volume":"32","author":"Fedorenko","year":"2012","journal-title":"Oncogene"},{"year":"2015","series-title":"Discovery of 1-(3, 3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino) pyrido [2, 3-d] pyrimidin-6-yl) phenyl) Urea (LY3009120) as a pan-RAF Inhibitor With Minimal Paradoxical Activation and Activity against BRAF or RAS Mutant Tumor Cells","author":"Henry","key":"10.1016\/j.lfs.2017.06.021_bb0110"},{"key":"10.1016\/j.lfs.2017.06.021_bb0115","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1158\/1535-7163.MCT-15-0262","article-title":"BGB-283, a novel RAF kinase and EGFR inhibitor, displays potent antitumor activity in BRAF-mutated colorectal cancers","volume":"14","author":"Tang","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.lfs.2017.06.021_bb0120","first-page":"46","volume":"A2","author":"Shim","year":"2012"},{"key":"10.1016\/j.lfs.2017.06.021_bb0125","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.bbrc.2011.12.061","article-title":"The role of autophagy in cytotoxicity induced by new oncogenic B-Raf inhibitor UI-152 in v-Ha-ras transformed fibroblasts","volume":"417","author":"Ahn","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.lfs.2017.06.021_bb0130","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/bkcs.10917","article-title":"Discovery of a highly specific and potent pan-RAF inhibitor","volume":"37","author":"Hong","year":"2016","journal-title":"Bull. Kor. Chem. Soc."},{"key":"10.1016\/j.lfs.2017.06.021_bb0135","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nature09454","article-title":"Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma","volume":"467","author":"Bollag","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2017.06.021_bb0140","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1021\/bi802067u","article-title":"The crystal structure of BRAF in complex with an organoruthenium inhibitor reveals a mechanism for inhibition of an active form of BRAF kinase","volume":"48","author":"Xie","year":"2009","journal-title":"Biochemistry"},{"key":"10.1016\/j.lfs.2017.06.021_bb0145","doi-asserted-by":"crossref","first-page":"7332","DOI":"10.1021\/jm300613w","article-title":"Conformation-specific effects of Raf kinase inhibitors: miniperspective","volume":"55","author":"Wang","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.lfs.2017.06.021_bb0150","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nbt1358","article-title":"A quantitative analysis of kinase inhibitor selectivity","volume":"26","author":"Karaman","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0155","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1158\/0008-5472.CAN-10-0646","article-title":"RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models","volume":"70","author":"Yang","year":"2010","journal-title":"Cancer Res."},{"key":"10.1016\/j.lfs.2017.06.021_bb0160","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1038\/sj.bjc.6605714","article-title":"Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy","volume":"102","author":"Paraiso","year":"2010","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0165","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.ccr.2012.10.009","article-title":"Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas","volume":"22","author":"Lito","year":"2012","journal-title":"Cancer Cell"},{"key":"10.1016\/j.lfs.2017.06.021_bb0170","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1016\/S1470-2045(12)70539-9","article-title":"Which drug, and when, for patients with BRAF-mutant melanoma?","volume":"14","author":"Jang","year":"2013","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0175","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1056\/NEJMoa1103782","article-title":"Improved survival with vemurafenib in melanoma with BRAF V600E mutation","volume":"364","author":"Chapman","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.lfs.2017.06.021_bb0180","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0140-6736(12)60868-X","article-title":"Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial","volume":"380","author":"Hauschild","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.lfs.2017.06.021_bb0185","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nature04304","article-title":"BRAF mutation predicts sensitivity to MEK inhibition","volume":"439","author":"Solit","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2017.06.021_bb0190","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1200\/JCO.2007.15.7636","article-title":"Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma","volume":"27","author":"Hauschild","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0195","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/sj.bjc.6603291","article-title":"Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis","volume":"95","author":"Eisen","year":"2006","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0200","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature08833","article-title":"RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth","volume":"464","author":"Hatzivassiliou","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2017.06.021_bb0205","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature08902","article-title":"RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF","volume":"464","author":"Poulikakos","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.lfs.2017.06.021_bb0210","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrc2559","article-title":"Targeting cancer with small molecule kinase inhibitors","volume":"9","author":"Zhang","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.lfs.2017.06.021_bb0215","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrclinonc.2011.69","article-title":"BRAF targeted therapy changes the treatment paradigm in melanoma","volume":"8","author":"Ribas","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.lfs.2017.06.021_bb0220","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1158\/1078-0432.CCR-11-1446","article-title":"Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents","volume":"19","author":"Mao","year":"2013","journal-title":"Clin. Cancer Res."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320517303077?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320517303077?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T10:56:44Z","timestamp":1535713004000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320517303077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":44,"alternative-id":["S0024320517303077"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2017.06.021","relation":{},"ISSN":["0024-3205"],"issn-type":[{"type":"print","value":"0024-3205"}],"subject":[],"published":{"date-parts":[[2017,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of a novel pan-RAF inhibitor with potent anti-tumor activity in preclinical models of BRAFV600E mutant cancer","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2017.06.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}