N-(3-Ethynyl-2,4-difluorophenyl)sulfonamide Derivatives as Selective Raf Inhibitors.
A series of N-(3-ethynyl-2,4-difluorophenyl)sulfonamides were identified as new selective Raf inhibitors. The compounds potently inhibit B-Raf(V600E) with low nanomolar IC50 values and exhibit excellent target specificity in a selectivity profiling investigation against 468 kinases. They strongly suppress proliferation of a panel of human cancer cell lines and patient-derived melanoma cells with B-Raf(V600E) mutation while being significantly less potent to the cells with B-Raf(WT). The compounds also display favorable pharmacokinetic properties with a preferred example (3s) demonstrating significant in vivo antitumor efficacy in a xenograft mouse model of B-Raf(V600E) mutated Colo205 human colorectal cancer cells, supporting it as a promising lead compound for further anticancer drug discovery.
['Li|Yingjun|Y|', 'Cheng|Huimin|H|', 'Zhang|Zhang|Z|', 'Zhuang|Xiaoxi|X|', 'Luo|Jinfeng|J|', 'Long|Huoyou|H|', 'Zhou|Yang|Y|', 'Xu|Yong|Y|', 'Taghipouran|Rana|R|', 'Li|Dan|D|', 'Patterson|Adam|A|', 'Smaill|Jeff|J|', 'Tu|Zhengchao|Z|', 'Wu|Donghai|D|', 'Ren|Xiaomei|X|', 'Ding|Ke|K|']
melanoma B-Raf colon cancer kinase inhibitor targeted therapy