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 14 days in vitro (DIV14), TTBK1-IN-1 was evaluated for its effects on neurite length. Acute exposure (up to 1 hour) across concentrations of 0.0625 to 100 μM did not alter neurite length. However, chronic exposure for 6 to 24 hours significantly reduced neurite length at 50 and 100 μM concentrations, with effects seen between 12 to 18 hours post-treatment[1].

TTBK1-IN-1 (intraperitoneal injection; doses of 2.5, 7, 20, 60, and 180 mg/kg administered 5 minutes prior to isoflurane treatment) significantly reduces tau phosphorylation at disease-relevant sites in vivo, particularly at the 180 mg/kg dosage. Additionally, a dose-dependent reduction in tau phosphorylation levels at Ser 422 was observed, with a 21% decrease at 20 mg/kg and a 60% decrease at 60 mg/kg, compared to the vehicle-treated control, in a mouse model of isoflurane-induced hypothermia[1].