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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.

SUBMITTER: Li Y

PROVIDER: S-EPMC4434482 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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N-(3-Ethynyl-2,4-difluorophenyl)sulfonamide Derivatives as Selective Raf Inhibitors.

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

ACS medicinal chemistry letters 20150318 5

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 compound ...[more]

PMID: 26005530

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