TTBK1-IN-1 是一种强效、选择性、脑渗透型 tau 微管蛋白激酶 1 (TTBK1) 抑制剂，IC50 为 2.7 nM。TTBK1-IN-1 可用于阿尔茨海默病及相关疾病的研究。
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[1].
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 pothermia mice model[1].
[1]. 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.
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