Design and synthesis of a potent inhibitor of class 1 DYRK kinases as a suppressor of adipogenesis

摘要: Dysregulation of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) has been demonstrated in several pathological conditions, including Alzheimer's disease and cancer progression. It recently reported that a gain function-mutation the human DYRK1B gene exacerbates metabolic syndrome by enhancing obesity. In previous study, we developed an inhibitor DYRK family kinases (INDY) INDY suppresses phenotypes induced overexpression DYRK1A or cellular animal models. this designed synthesized novel based on crystal structure DYRK1A/INDY complex replacing phenol group with dibenzofuran to produce derivative, named BINDY. This compound exhibited potent selective inhibitory activity toward vitro assay. Furthermore, treatment 3T3-L1 pre-adipocytes BINDY hampered adipogenesis suppressing expression critical transcription factors PPARγ C/EBPα. study indicates possibility as potential drug for syndrome.