DYRK1A/B Inhibitor AnnH75

Pale yellow solid. Soluble in DMSO. Potent selective membrane-permeable DYRK1A (IC50=181nM) and DYRK1B inhibitor. Off-target inhibition of CLK1, CLK4 and Haspin/GSG2, Shows no inhibitory effects on monoamine oxidase A (MAO A), Inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency, Dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4 and tau) without negative effects on cell viability in celular assays, Moderate inhibitor of CDK8, CLK2, GRK4, MEK2, PIM1, PIM3 and PKCepsilon, Shows minimal cytotoxic effects in HeLa and PC12 cells up to 10µM, The pleiotropic protein kinase DYRK1A has diverse functions in cell cycle control, neuronal differentiation and synaptic transmission and has attracted increasing interest as a potential drug target, due to its role in the pathology of Down syndrome, neurodegenerative diseases such as Alzheimer's disease and cancer. The closely related kinase DYRK1B has been associated with cancer cell survival by arresting cells in a quiescent state to allow cellular repair and mutations in DYRK1B might be causative in metabolic syndrome.