AD-35 (free base)

AD-35 free base is an orally active, blood-brain barrier-permeable acetylcholinesterase inhibitor with an IC₅₀ of 793 nM. AD-35 free base inhibits metal-induced amyloid-β aggregation and disassembles preformed amyloid-β aggregates. In rat models of cognitive impairment, AD-35 free base attenuates Aβ_25-35-induced astrocyte activation, TNF-α and IL-1β release, inhibits ERK phosphorylation, and alleviates learning and memory deficits. AD-35 free base can be used for research on Alzheimer's disease^[1]. In Vitro:AD-35 (pre-incubated for 10 min, incubated with substrate for 15 min) free base moderately inhibits purified acetylcholinesterase (IC₅₀ = 793 nM) and butyrylcholinesterase (IC₅₀ = 31428 nM) in vitro, and exhibits activity preference for acetylcholinesterase^[1].
AD-35 (20 μM; 10 min) free base effectively chelates Cu²⁺ and Fe³⁺ in vitro, but exhibits extremely weak chelating activity towards Zn^2+[1].
AD-35 (6-10 μM; 5 h) free base weakly promotes Cu²⁺ transport into human neuroblastoma SH-SY5Y cells in vitro^[1].
AD-35 (24 h) free base potently inhibits Cu²⁺-induced Aβ₁-₄₂ aggregation in a concentration-dependent manner in vitro, exerts only weak inhibitory effects on the spontaneous aggregation of Aβ₁-₄₂, and effectively disassembles preformed Cu²⁺-induced Aβ_1-42 aggregates^[1]. In Vivo:AD-35 (0.5-10 mg/kg; p.o.; once daily; for 28 consecutive days) free base dose-dependently improves Aβ_25-35 (HY-P0128)-induced cognitive impairment in SD rats, reduces the production of pro-inflammatory cytokines, inhibits astrocyte activation, and suppresses the phosphorylation of ERK in hippocampal tissues^[1].