Compound AK-2, also known as hAChE/hBACE-1-IN-4, is a quinazoline derivative that demonstrates significant inhibitory activity against the enzymes hAChE and hBACE-1 (hAChE, IC 50 = 0.283 μM; hBACE-1, IC 50 = 0.231 μM). This compound also shows potential in inhibiting Aβ aggregation and possesses characteristics such as non-neurotoxicity, blood-brain barrier permeability, and oral activity, making it a valuable agent for research in Alzheimer's disease [1].

BCHE (human):0.231 μM, AChE (human):0.283 μM

hAChE/hBACE-1-IN-4, tested at concentrations of 10, 20, 40, and 80 μM over 24 hours, exhibits non-neurotoxic properties [1]. In the Cell Viability Assay [1] using the SH-SY5Y cell line, this compound resulted in a 26% reduction in cell viability at the highest concentration of 80 μM.

hAChE/hBACE-1-IN-4, administered at 500 mg/kg orally for 14 days, demonstrates a significant safety margin in Wistar rats, indicating its potential for further in vivo studies [1]. When given at 500 mg/kg orally for 9 days, this compound inhibits BACE-1 activity, alleviating cognitive deficits and exhibiting anti-aβ effects at the tested dosage in Wistar rats [1]. Additionally, hAChE/hBACE-1-IN-4, at 500 mg/kg by oral gavage for 4 days, shows the ability to cross the blood-brain barrier, reaching specific target sites in brain tissue [1]. Animal Model: Wistar rats [1] Dosage: 500 mg/kg for 14 days Administration: Oral gavage (p.o.) Result: Renal and hepatic functional parameters remained within normal limits, and tissue appearances were normal in kidneys, heart, liver, and brain. Animal Model: Wistar rats [1] Dosage: 20 mg/kg for 9 days Administration: Oral gavage (p.o.) Result: ELT decreased, and total platform crossings increased compared to the diseased model group, with enhancements in neuronal density and arrangement. Animal Model: Wistar rats [1] Dosage: 10 and 20 mg/kg for 4 days Administration: i.g. Result: AK-2 concentrations in brain homogenates were 0.633 and 0.977 μg/mL.