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Anti-cancer effects of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one derivatives on hepatocellular carcinoma harboring FGFR4 activation
DC Field | Value | Language |
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dc.contributor.author | 심태보 | - |
dc.date.accessioned | 2022-03-11T05:53:11Z | - |
dc.date.available | 2022-03-11T05:53:11Z | - |
dc.date.issued | 2022-01 | - |
dc.identifier.issn | 1522-8002 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/187850 | - |
dc.description.abstract | Hepatocellular carcinoma (HCC) is disease with a high mortality rate and limited treatment options. Alterations of fibroblast growth factor receptor 4 (FGFR4) has been regarded as an oncogenic driver for HCC and a promising target for HCC therapeutics. Herein, we report that GNF-7, a multi-targeted kinase inhibitor, and its derivatives including SIJ1263 (IC50 < 1 nM against FGFR4) are highly potent FGFR4 inhibitors and are capable of strongly suppressing proliferation of HCC cells and Ba/F3 cells transformed with wtFGFR4 or mtFGFR4. Compared with known FGFR4 inhibitors, both GNF-7 and SIJ1263 possess much higher (up to 100-fold) anti-proliferative activities via FGFR signaling blockade and apoptosis on HCC cells. Especially, SIJ1263 is 80-fold more potent (GI50 = 24 nM) on TEL-FGFR4 V550E Ba/F3 cells than BLU9931, which suggests that SIJ1263 would be effective for overriding drug resistance. In addition, both substances strongly suppress migration/invasion and colony formation of HCC cells. It is worth noting that SIJ1263 is superior to GNF-7 with regards to the fact that activities of SIJ1263 are higher than those of GNF-7 in all assays performed in this study. Collectively, this study provides insight into designing highly potent FGFR4 inhibitors capable of potentially overcoming drug-resistance for the treatment of HCC patients. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Neoplasia Press | - |
dc.relation.isPartOf | NEOPLASIA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Anti-cancer effects of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one derivatives on hepatocellular carcinoma harboring FGFR4 activation | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | BioMedical Science Institute (의생명과학부) | - |
dc.contributor.googleauthor | Yunju Nam | - |
dc.contributor.googleauthor | Injae Shin | - |
dc.contributor.googleauthor | Younghoon Kim | - |
dc.contributor.googleauthor | Seong Shick Ryu | - |
dc.contributor.googleauthor | Namdoo Kim | - |
dc.contributor.googleauthor | Eunhye Ju | - |
dc.contributor.googleauthor | Taebo Sim | - |
dc.identifier.doi | 10.1016/j.neo.2021.11.011 | - |
dc.contributor.localId | A05926 | - |
dc.relation.journalcode | J02312 | - |
dc.identifier.eissn | 1476-5586 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1476558621001019 | - |
dc.subject.keyword | FGFR4 kinase | - |
dc.subject.keyword | HCC | - |
dc.subject.keyword | FGFR4 inhibitor | - |
dc.subject.keyword | GNF-7 | - |
dc.subject.keyword | SAR | - |
dc.contributor.alternativeName | Sim, Taebo | - |
dc.contributor.affiliatedAuthor | 심태보 | - |
dc.citation.volume | 24 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 34 | - |
dc.citation.endPage | 49 | - |
dc.identifier.bibliographicCitation | NEOPLASIA, Vol.24(1) : 34-49, 2022-01 | - |
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