AChE/GSK-3β-IN-1

AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research[1].

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ROS

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Neurological Disease

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

Signaling Pathways >> Neuronal Signaling >> AChE

AChE/GSK-3β-IN-1 (compound GT15) (300 nM) has strong binding affinities with GSK3 family and exhibits a potent inhibitory activity against dual tyrosine phospho-regulated kinase 1 (DYRK1) (DYRK1α and DYRK1β with IC50 of 28.3 nM and 119.7 nM, respectively)[1]. AChE/GSK-3β-IN-1 (compound GT15) (5-15 µM; 1 hours; N2a-tau cells) exhibits good permeability across the blood-brain-barrier and ability to inhibit the phosphorylation of tau protein[1]. AChE/GSK-3β-IN-1 (compound GT15) (5 µM; BV2 cells) prevents the increase of ROS caused by LPS and reduces oxidative stress[1]. Western Blot Analysis[1] Cell Line: N2a-tau cells Concentration: 5, 10, and 15 µM Incubation Time: 6 hours Result: Decreased the level of phosphorylated tau protein was reduced to 49% at 5 µM and 17% at 15 µM.

AChE/GSK-3β-IN-1 (compound GT15) (15 mg/kg,; p.o.; ICR male mice) has a function of improving memory and cognition in mice[1]. Animal Model: ICR male mice[1] Dosage: 15 mg/kg Administration: Oral administration Result: Improved the cognitive impairment of the mice.

[1]. Jiang X, et, al. Rational design and biological evaluation of a new class of thiazolopyridyl tetrahydroacridines as cholinesterase and GSK-3 dual inhibitors for Alzheimer's disease. Eur J Med Chem. 2020 Dec 1;207:112751.