Probing the ATP-Binding Pocket of Protein Kinase Dyrk1A with Benzothiazole Fragment Molecules

摘要: DYRK1A has emerged as a potential target for therapies of Alzheimer’s disease using small molecules. On the basis observation selective inhibition by firefly d-luciferin, we have explored static and dynamic structural properties fragment sized variants benzothiazole scaffold with respect to X-ray crystallography NMR techniques. The compounds excellent ligand efficiencies show remarkable diversity binding modes in equilibrium. Binding geometries are determined part interactions often considered “weak”, including “orthogonal multipolar” types represented by, example, F–CO, sulfur–aromatic, halogen–aromatic interactions, together hydrogen bonds that modulated variation electron withdrawing groups. These studies how is highly promising development therapeutic inhibitors. In addition, subtleties dynamics, full struct...