DYRK1A/B Inhibitor AnnH31

Off-white to tan solid. Soluble in DMSO. Potent selective membrane-permeable DYRK1A (IC50=81nM) and DYRK1B inhibitor. Off-target inhibition of CLK1 and slightly DYRK2 and HIPK2, Shows minimal inhibitory effects on monoamine oxidase A (MAO A) (IC50=3.2µg), with 40-fold selectivity for DYRK1A over MAO A, Dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4 and tau) without negative effects on cell viability in celular assays, Shows cytotoxic effects in HeLa cells at high concentrations (3-10µM), 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.