Compound 43 TAO Kinase Inhibitor

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An inhibitor of TAOKs (IC50s = 11 and 15 nM for TAOK1 and TAOK2, respectively); selective for TAOK1 and TAOK2 over 62 kinases in a panel, but does inhibit TAOK3 by 87% and seven additional kinases by 21-52%; inhibits proliferation of SK-BR-3, BT-549, and MCF-7 cells by 94, 82, and 46%, respectively, at a concentration of 10 µM; reduces tau phosphorylation in kinase assays at 5-60 µM and in HEK293 cells at 5, 10, and 30 µM; reduces tau phosphorylation in cortical neurons in a transgenic mouse model of tauopathy and in induced pluripotent stem cell-derived neurons from patients with frontotemporal lobar degeneration