A novel small molecule RK-019 inhibits FGFR2-amplification gastric cancer cell proliferation and induces apoptosis in vitro and in vivo

Gastric cancer (GC) is one of the most malignant cancers and is estimated to be fifth in incidence ratio and the third leading cause of cancer death worldwide. Despite advances in GC treatment, poor prognosis and low survival rate necessitate the development of novel treatment options. Fibroblast gr...

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Main Authors: Jun Zeng (Author), Kai Ran (Author), Xinyue Li (Author), Longyue Tao (Author), Qiwei Wang (Author), Jiangtao Ren (Author), Rong Hu (Author), Yongxia Zhu (Author), Zhihao Liu (Author), Luoting Yu (Author)
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Published: Frontiers Media S.A., 2022-09-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Jun Zeng  |e author 
700 1 0 |a Kai Ran  |e author 
700 1 0 |a Xinyue Li  |e author 
700 1 0 |a Longyue Tao  |e author 
700 1 0 |a Qiwei Wang  |e author 
700 1 0 |a Jiangtao Ren  |e author 
700 1 0 |a Rong Hu  |e author 
700 1 0 |a Yongxia Zhu  |e author 
700 1 0 |a Zhihao Liu  |e author 
700 1 0 |a Luoting Yu  |e author 
245 0 0 |a A novel small molecule RK-019 inhibits FGFR2-amplification gastric cancer cell proliferation and induces apoptosis in vitro and in vivo 
260 |b Frontiers Media S.A.,   |c 2022-09-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2022.998199 
520 |a Gastric cancer (GC) is one of the most malignant cancers and is estimated to be fifth in incidence ratio and the third leading cause of cancer death worldwide. Despite advances in GC treatment, poor prognosis and low survival rate necessitate the development of novel treatment options. Fibroblast growth factor receptors (FGFRs) have been suggested to be potential targets for GC treatment. In this study, we report a novel selective FGFR inhibitor, RK-019, with a pyrido [1, 2-a] pyrimidinone skeleton. In vitro, RK-019 showed excellent FGFR1-4 inhibitory activities and strong anti-proliferative effects against FGFR2-amplification (FGFR2-amp) GC cells, including SNU-16 and KATO III cells. Treatment with RK-019 suppressed phosphorylation of FGFR and its downstream pathway proteins, such as FRS2, PLCγ, AKT, and Erk, resulting in cell cycle arrest and induction of apoptosis. Furthermore, daily oral administration of RK-019 could attenuate tumor xenograft growth with no adverse effects. Here, we reported a novel specific FGFR inhibitor, RK-019, with potent anti-FGFR2-amp GC activity both in vitro and in vivo. 
546 |a EN 
690 |a gastric cancer 
690 |a receptor tyrosine kinase 
690 |a antineoplastic agents 
690 |a FGFRs 
690 |a cell apoptosis 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 13 (2022) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2022.998199/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/b5b2d480140b4a5d93c73896a3a1f42d  |z Connect to this object online.