A Novel Tgf-Beta Receptor I Kinase Inhibitor Demonstrated To Be An Effective Immuno-Therapy For Cancer

TGF-beta (TGF-β) pathways, despite serving as tumor suppressor in early stage of carcinogenesis, have shown be one of the key tumor-promoting factors in later-stage tumor progression. TGF-β receptor I kinase (TGF-βR1) inhibitors have shown great potentials in their anti-tumor and anti-metastasis efficacy in preclinical studies and some of them are being tested in the clinical settings. A specific TGF-βR1 inhibitor YL-13027 was developed at Yingli Pharmaceutical. YL-13027 possesses good ADME and PK properties and shows potent inhibition of the TGF-β and receptor interaction both in cell-free and cell-based assays. Functionally, in vitro Treg differentiation assay demonstrated the significant inhibition of the induction of FoxP3 expressing cells as well as inhibiting the secretion of IL-10 by YL-13027. In murine colon cancer CT26 model, YL-13027 was well tolerated and significantly inhibited tumor progression with dose dependency. More mechanistic studies are on-going. These data suggest that YL-13027, a novel TGF-βR1 inhibitor, represents a promising and safe immune modulator and shows great potential as a cancer immuno-therapeutics. Citation Format: Zusheng Xu, Yangtong Lou, Li Chen, Kun Zeng, Qingrui Sun, Yingying Qu, Wei Wang, Xiaodong Wu, Xiaomei Ge, Ying Gu, Yingjia Zhang, He Zhou. A novel TGF-beta receptor I kinase inhibitor demonstrated to be an effective immuno-therapy for cancer [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 4568. doi:10.1158/1538-7445.AM2017-4568