TTBK1-IN-1 (compound 31) is a potent and selective tau microtubule protein kinase 1 (TTBK1) inhibitor (IC50=315 nM) with central nervous system (CNS) penetration that inhibits tau phosphorylation at the disease-associated Ser 422 epitope, and can be used to study Alzheimer's disease.

In primary mouse neurons at DIV14, short-term treatment (1 hour) with TTBK1-IN-1 at concentrations from 0.0625 to 100 μM had no effect on neurite length. However, longer exposures (6-24 hours) at the same concentration range led to a significant reduction in neurite length starting around 12-18 hours after treatment[1].

In mice, intraperitoneal injection of TTBK1-IN-1 (2.5-180 mg/kg, given 5 min before isoflurane exposure) significantly reduced tau phosphorylation at Ser422 in the brain at 180 mg/kg. A dose-dependent trend was also observed: 20 mg/kg reduced p-Ser422 levels by 21%, while 60 mg/kg led to a 60% reduction, in a model of isoflurane-induced hypothermia[1].