Identification of protein kinase fibroblast growth factor receptor 1 (FGFR1) inhibitors among the derivatives of 5-(5,6-dimethoxybenzim idazol-1-yl)-3-hydroxythiophene-2-carboxylic acid

摘要

Fibroblast growth factor receptor 1 (FGFR1) plays an important role in tumorigenesis, suggesting that inhibitors of this protein kinase may become important compounds for the development of anticancer agents. Using molecular docking approach, we have identified a novel class of FGFR1 inhibitors belonging to the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)3-hydroxythiophene-2-carboxylic acid. It was revealed that the most promising compound 5-(5,6-dimethoxybenzimidazol-1-yl)-3-[2-(methanesulfonyl)benzyloxy]thiophene-2-carboxylic acid methyl ester inhibits FGFR1 with an IC50 value of 150 nM in in vitro kinase assay. The structure-activity relationships have been studied, and the binding mode of this chemical class has been proposed.