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Overview
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Background
AZD3839 is a novel inhibitor of BACE1 with IC50 value of 4.8μM [1].AZD3839 has been reported to inhibit human BACE1 activity in a biochemical FRET assay. In addition, AZD3839 has also been reported to inhibit the release of sAPPβs from human SH-SY5Y cells, mouse N2A cells and mouse and guinea pig primary cortical neurons. Moreover, AZD3839 has been revealed to effectively decrease the cerebrospinal fluid (CSF), plasma, and brain Aβ levels in guinea pig, mouse and non-human primate. AZD3839 has also been revealed to decrease the levels of Aβ40 secreted from C57BL/6 mouse primary cortical neurons, N2A cells (mouse neuroblastoma), and Dunkin-Hartley guinea pig primary cortical neurons, with IC50 values of 50.9, 32.2, and 24.8 nmol/liter, respectively [2].
[1] Sparve E1, Quartino AL1, Luttgen M1, Tunblad K1, Teiling-Gardlund A1, Falting J1, Alexander R1, Kagstrom J1, Sjodin L1, Bulgak A1, Al-Saffar A1, Bridgland-Taylor M2, Pollard C3, Swedberg MD4, Vik T5, Paulsson B1. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on Single Ascending Dose study data with AZD3839. J Pharmacol Exp Ther. 2014 Jun 10.
[2] Jeppsson F1, Eketjäll S, Janson J, Karlström S, Gustavsson S, Olsson LL, Radesäter AC, Ploeger B, Cebers G, Kolmodin K, Swahn BM, von Berg S, Bueters T, Fälting J. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57.
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