TTBK1-IN-1

• CAT Number: I044525
• CAS Number: 2735015-60-6
• Molecular Formula: C18H19N5O2
• Molecular Weight: 337.38
• Purity: ≥95%
• Synonyms: (3S)-1-[1-(2-amino-6-methoxypyrimidin-4-yl)pyrrolo[3,2-c]pyridin-6-yl]-3-methylpent-1-yn-3-ol
• InChI: InChI=1S/C18H19N5O2/c1-4-18(2,24)7-5-13-9-14-12(11-20-13)6-8-23(14)15-10-16(25-3)22-17(19)21-15/h6,8-11,24H,4H2,1-3H3,(H2,19,21,22)/t18-/m0/s1
• InChIKey: HPJVZSVEIGCFJP-SFHVURJKSA-N
• SMILES: CCC(C)(C#CC1=CC2=C(C=CN2C3=CC(=NC(=N3)N)OC)C=N1)O

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]. TTBK1-IN-1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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].

Reference

[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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