title: N-(3-Ethynyl-2,4-difluorophenyl)sulfonamide Derivatives as Selective Raf Inhibitors.
abstract: 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.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China ; University of Chinese Academy of Sciences , #19 Yuquan Road, Beijing 100049, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China ; Biotechnological Institute of Chinese Materia Medica and Department of Pharmacology, Jinan University , #601 Huangpu Avenue West, Guangzhou 510632, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Huoyou
authors.initials: H
authors.lastname: Long
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China ; University of Chinese Academy of Sciences , #19 Yuquan Road, Beijing 100049, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand.
authors.forename: Rana
authors.initials: R
authors.lastname: Taghipouran
authors.affiliation: Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand ; Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand.
authors.forename: Adam
authors.initials: A
authors.lastname: Patterson
authors.affiliation: Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand ; Auckland Cancer Society Research Centre and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , #92019 Private Bag, Auckland 1142, New Zealand.
authors.forename: Jeff
authors.initials: J
authors.lastname: Smaill
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , #190 Kaiyuan Avenue, Guangzhou 510530, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
keywords: B-Raf; colon cancer; kinase inhibitor; melanoma; targeted therapy