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A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration

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Abstract

Fibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activity in a gastric cancer xenograft tumor model by targeting FGFR1 signaling. These results show that L16H50 is a potent non-ATP-competitive FGFR1 inhibitor and may provide strong rationale for its evaluation in gastric cancer patients.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81402839, 81473242 and 81272462) the ZheJiang Province Natural Science Fund of China (Grant Nos. LY17H160059, LY14H160044) and the Technology Foundation for Medical Science of Zhejiang Province (Grant Nos. 2012KYA129), Granted by the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences.

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    Authors and Affiliations

    1. Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang, 325035, China

      Jianzhang Wu, Wulan Li, Yangyang Zhou, Encheng Bai, Yanting Kang, Qiuxiang Chen, Weitao Fu, Di Yun, Peihong Qiu, Yuepiao Cai & Guang Liang

    2. Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

      Xiaojing Du, Yangyang Zhou, Encheng Bai, Yanting Kang, Qiuxiang Chen & Rong Jin

    3. College of Information Science and Computer Engineering, the First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

      Wulan Li

    4. College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325035, China

      Qing Xu

    5. Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

      Rong Jin

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    1. Jianzhang Wu
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    Correspondence to Peihong Qiu, Rong Jin or Yuepiao Cai.

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    Jianzhang Wu, Xiaojing Du, Wulan Li and Yangyang Zhou have contributed to this work equally.

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    Wu, J., Du, X., Li, W. et al. A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration. Apoptosis 22, 852–864 (2017). https://doi.org/10.1007/s10495-017-1361-7

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