TTBK1-IN-1 is a highly potent and selective inhibitor of tau tubulin kinase 1 (TTBK1), capable of penetrating the blood-brain barrier with ease. With an IC 50 value of 2.7 nM, TTBK1-IN-1 exhibits strong inhibitory activity against TTBK1. This compound holds great promise for advancing research in Alzheimer's disease and other tauopathies.

In primary mouse neuronal cultures at DIV14, and analysis of neurite branching is used as a surrogate of neuron health. At acute timepoints (up to 1 h following administration), TTBK1-IN-1 (0.0625-100 μM; 1 hour) has no effect on neurite length when tested up to 100 μM. At chronic effects test, TTBK1-IN-1 (0.0625-100 μM; 6-24 hours) cause a significant decrease in neurite length at the 50 and 100 μM concentrations beginning at 12–18 h following treatment[1].

TTBK1-IN-1 (intraperitoneal?injection; 2.5, 7, 20, 60, and 180 mg/kg; 5 min prior to isoflurane treatment) significantly decreases in vivo tau phosphorylation at disease-relevant sites at 180 mg/kg. And there is a trend indicating a dose-responsive effect on tau phosphorylation levels at Ser 422 (20 mg/kg, 21% decrease and 60 mg/kg, 60% decrease, respectively, in tau phosphorylation at Ser 422 vs vehicle-treated control) in isoflurane-induced hypothermia mice model[1].