An inhibitor of BACE1 and 2
β-Secretase inhibitor IV is an inhibitor of β-site amyloid protein cleaving enzymes (BACE/β-secretase) 1 and 2 (IC50s = 15 and 230 nM for human BACE1 and 2, respectively). [1] It has >500-fold selectivity for BACE1 and 2 over the aspartyl proteases renin and cathepsin D. β-Secretase inhibitor IV inhibits secretion of amyloid-β (Aβ) precursor protein (APP; IC50 = 29 nM) in HEK293T cells transfected with a truncated APP. It also inhibits formation of the Aβ peptides Aβ38, Aβ40, and Aβ42 in primary chick neurons (IC50s = 3.7, 4.7, and 4.8 nM, respectively).[2]
Reference:
[1.] Stachel, S.J., Coburn, C.A., Steele, T.G., et al. Structure-based design of potent and selective cell-permeable inhibitors of human ?-secretase (BACE-1). Journal of Medicinal Chemistry 47(26), 6447-6450 (2004).
[2]. Czvitkovich, S., Duller, S., Mathiesen, E., et al. Comparison of pharmacological modulation of APP metabolism in primary chicken telencephalic neurons and in a human neuroglioma cell line. J. Mol. Neurosci. 43(3), 257-267 (2011).
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