Abstract 4187: Preclinical evaluation of sulfatinib, a novel angio-immuno kinase inhibitor targeting VEGFR, FGFR1 and CSF1R kinases

Both vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) singling pathways can mediate tumor angiogenesis. Colony stimulating factor 1 receptor (CSF1R) plays an important role on functions of macrophages. Recently the roles of the VEGFR, FGFR and CSF1R in regulation of T cells, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells, thereby increasing tumor immune evasion, have been demonstrated[1-3]. Therefore, blockade of tumor angiogenesis and tumor immune evasion by simultaneously targeting VEGFR, FGFR and CSF1R kinases may represent a promising approach for anti-cancer therapy. We report here the preclinical studies for sulfatinib (HMPL-012), a potent and highly selective small molecule tyrosine kinase inhibitor against VEGFR, FGFR1 and CSF1R. Sulfatinib inhibited VEGFR1, 2, and 3, FGFR1 and CSF1R kinases with IC50s in a range of 1~24 nM, and it strongly blocked VEGF induced VEGFR2 phosphorylation in HEK293KDR cells and CSF1 stimulated CSF1R phosphorylation in RAW264.7 cells with IC50 of 2 and 79 nM, respectively. Sulfatinib also attenuated VEGF or FGF stimulated HUVEC cells proliferation with IC50 Citation Format: jinghong Zhou, Jun Ni, Min Cheng, Na Yang, Junqing Liang, Liang Ge, Wei Zhang, Jianxing Tang, qiaoling Sun, Fu Li, Jia Hu, Dongxia Shi, Hongbo Chen, Jingwen Long, Junen Sun, Fang Yin, Xuelei Ge, Hong Jia, Feng Zhou, Yongxin ren, Weiguo Qing, Weiguo Su. Preclinical evaluation of sulfatinib, a novel angio-immuno kinase inhibitor targeting VEGFR, FGFR1 and CSF1R kinases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2017-4187