Identification of CLK1 Inhibitors by a Fragment-linking Based Virtual Screening (original) (raw)

Molecular Informatics, 2016

Abstract

Alternative splicing plays an important role in the regulation of protein biosynthesis. CDC2-like kinases (CLKs) phosphorylate splicing factors rendering them a potential target for treating diseases caused by splicing dysregulation. As selective and potent inhibitors of CLK1 are still lacking, a fragment-linking based virtual screening campaign was successfully applied to identify new inhibitors showing activity on CLK1. These inhibitors exhibit a novel 2,4-substituted 1,3-thiazole scaffold that is suitable for further modification. A subsequently performed docking and protein structure based analysis revealed first hints for inhibitors showing preferred binding activity for CLK1 and DYRK2 over other splicing kinases.

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