(S)-(-)-Anatabine

(S)-(-)-Anatabine is an NFκB/BACE-1 inhibitor with blood-brain barrier penetration. (S)-(-)-Anatabine inhibits NFκB activation via phosphorylation of its p65 subunit. (S)-(-)-Anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels. (S)-(-)-Anatabine lowers production of Aβ_1-40 and Aβ_1-42 by reducing β-cleavage of amyloid precursor protein without affecting α-cleavage. (S)-(-)-Anatabine can be used for the research of Alzheimer's disease^[1][2]. In Vitro:(S)-(-)-Anatabine (24 h) dose-dependently reduces Aβ_1-40 and Aβ_1-42 production with an IC₅₀ of 640 μg/mL^[1].
(S)-(-)-Anatabine (200-800 μg/mL; 3 h) dose-dependently inhibits TNFα-induced NFκB activation in HEK293 NFκB luciferase reporter cells^[1].
(S)-(-)-Anatabine (600 μg/mL; 24 h) inhibits basal p65 NFκB phosphorylation in 7W CHO cells overexpressing human APP, and inhibits TNFα-induced p65 NFκB phosphorylation in HEK293 and SHSY-5Y cells^[1].
(S)-(-)-Anatabine (500-1000 μg/mL; 30 min) fully inhibits TNFα-induced BACE-1 transcription in human neuronal-like SHSY-5Y cells^[1].
(S)-(-)-Anatabine (5-1000 μg/mL; 24 h) dose-dependently reduces BACE-1 protein levels in human neuronal-like SHSY-5Y cells^[1]. In Vivo:(S)-(-)-Anatabine (2 mg/kg; i.p.; single dose) can cross the blood–brain barrier, with the area under the curve (AUC)
and the maximal concentration (C_max) achieving approximately 3.5 times greater in the brain of B6/SJL F1 mice than in the plasma^[1].