Discovery of N-(3-((1-Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide (CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs).

@article{Wang2016DiscoveryON,
  title={Discovery of N-(3-((1-Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide (CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs).},
  author={Qiang Wang and Feiyang Liu and Beilei Wang and Fengming Zou and Cheng Chen and Xiaochuan Liu and Aoli Wang and Shuang S. Qi and Wenchao Wang and Ziping Qi and Zheng Nan Zhao and Zhenquan Hu and Wei Wang and Li Wang and Shanchun Zhang and Yuexiang Wang and Jing Liu and Qingsong Liu},
  journal={Journal of medicinal chemistry},
  year={2016},
  volume={59 8},
  pages={
          3964-79
        }
}
c-KIT kinase is a validated drug discovery target for gastrointestinal stromal tumors (GISTs). Clinically used c-KIT kinase inhibitors, i.e., Imatinib and Sunitinib, bear other important targets such as ABL or FLT3 kinases. Here we report our discovery of a more selective c-KIT inhibitor, compound 13 (CHMFL-KIT-110), which completely abolished ABL and FLT3 kinase activity. KinomeScan selectivity profiling (468 kinases) of 13 exhibited a high selectivity (S score (1) = 0.01). 13 displayed great… CONTINUE READING
BETA
5
Twitter Mentions