somcl085anovelmultitargetedfgfrinhibitordisplayspotentanticanceractivityinfgfraddictedhumancancermodels
文献类型：期刊论文
| 作者 | Jiang Xifei1; Dai Yang2; Peng Xia2; Shen Yanyan2; Su Yi2; Wei Manman2; Liu Weiren1; Ding Zhenbin1; Zhang Ao2 ; Shi Yinghong1
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| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2018 |
| 卷号 | 39期号:2页码:243 |
| 关键词 | human cancer anticancer drug SOMCL-085 receptor tyrosine kinase FGFR xenograft nude mouse model |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.96 |
| 英文摘要 | Aberrant fibroblast growth factor receptor (FGFR) activation is found across a diverse spectrum of malignancies, especially those lacking effective treatments. SOMCL-085 is a novel FGFR-dominant multi-target kinase inhibitor. Here, we explored the FGFR-targeting anticancer activity of SOMCL-085 both in vitro and in vivo. Among a panel of 20 tyrosine kinases screened, SOMCL-085 potently inhibited FGFR1, FGFR2 and FGFR3 kinase activity, with IC_(50) values of 1.8,1.9 and 6.9 nmol/L, respectively. This compound simultaneously inhibited the angiogenesis kinases VEGFR and PDGFR,but without obvious inhibitory effect on other 12 tyrosine kinases. In 3 representative human cancer cell lines with different mechanisms of FGFR activation tested, SOMCL-085 (20-500 nmol/L) dose-dependently inhibited FGFR1-3 phosphorylation and the phosphorylation of their key downstream effectors PLCγ and Erk. In 7 FGFR aberrant human cancer cell lines, regardless of the mechanistic complexity of FGFR over-activation, SOMCL-085 potently inhibited FGFR-driven cell proliferation by arresting cells at the G_1/S phase. In the FGFRl-amplified lung cancer cell line H1581 xenograft mice and FGFR2-amplified gastric cancer cell line SNU16 xenograft mice, oral administration of SOMCL-085 (25,50 mg.kg~(-1).d~(-1)) for 21 days substantially suppressed tumor growth without affecting their body-weight. These results suggest that SOMCL-085 is a potent multi-target FGFR inhibitor that inhibits the FGFR-dependent neoplastic phenotypes of human cancer cells in vitro and in vivo. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/285335]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.复旦大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Jiang Xifei,Dai Yang,Peng Xia,et al. somcl085anovelmultitargetedfgfrinhibitordisplayspotentanticanceractivityinfgfraddictedhumancancermodels[J]. actapharmacologicasinica,2018,39(2):243. |
| APA | Jiang Xifei.,Dai Yang.,Peng Xia.,Shen Yanyan.,Su Yi.,...&Al Jing.(2018).somcl085anovelmultitargetedfgfrinhibitordisplayspotentanticanceractivityinfgfraddictedhumancancermodels.actapharmacologicasinica,39(2),243. |
| MLA | Jiang Xifei,et al."somcl085anovelmultitargetedfgfrinhibitordisplayspotentanticanceractivityinfgfraddictedhumancancermodels".actapharmacologicasinica 39.2(2018):243. |
入库方式： OAI收割
来源：上海药物研究所
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