TTBK1-IN-1 is a potent, selective and brain-penetrant tau tubulin kinase 1 (TTBK1) inhibitor with an IC₅₀ of 2.7 nM. TTBK1-IN-1 can be used for the research of alzheimer’s disease and related 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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Tamara Halkina, et al. Discovery of Potent and Brain-Penetrant Tau Tubulin Kinase 1 (TTBK1) Inhibitors that Lower Tau Phosphorylation In Vivo. J Med Chem. 2021 May 13;64(9):6358-6380.  [Content Brief]