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ID: ALA3580536
Journal: ACS Med Chem Lett
Title: N-(3-Ethynyl-2,4-difluorophenyl)sulfonamide Derivatives as Selective Raf Inhibitors.
Authors: Li Y, Cheng H, Zhang Z, Zhuang X, Luo J, Long H, Zhou Y, Xu Y, Taghipouran R, Li D, Patterson A, Smaill J, Tu Z, Wu D, Ren X, Ding K.
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.
CiteXplore: 26005530