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

• DOI: 10.1007/s00706-019-02493-5
• Publication Date: 2019-09-28T10:02:36Z
• Authors: Galyna Volynets; Sergiy Lukashov; Iryna Borysenko; Andrii Gryshchenko; Sergiy Starosyla; Volodymyr Bdzhola; Tetiana Ruban; Anna Iatsyshyna; Lyubov Lukash; Yaroslav Bilokin; Sergiy Yarmoluk
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

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.