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Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening

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Open access
Authors
Xu, W.
Chen, G.
Zhu, W.
Zuo, Zhili
Date
2010
Collection
Type
Journal Article
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Abstract

Nowadays identification of novel non-peptide β-secretase (BACE-1, hereinafter) inhibitors with low cytotoxicity and good blood–brain barrier (BBB) property holds common interest of drug discovery for Alzheimer’s disease. Twenty SPECS compounds were tested in BACE-1 FRET assays and methylthiazoletetrazolium (MTT) cytotoxicity experiment. Two compounds: 2 and 15 demonstrated IC50 values of 0.53 and 9.4 μM. In addition, 2 showed least toxic effect to the neuroblastoma cells. The results from both in silico and in vitro studies provided new pharmacophoric entities for chemical synthesis and optimization on the current discovered BACE-1 small molecule inhibitors.

Citation
Xu, Weijun and Chen, Gang and Zhu, Weiliang and Zuo, Zhili. 2010. Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening. Bioorganic & Medicinal Chemistry Letters. 20 (19): pp. 5763-5766.
Source Title
Bioorganic & Medicinal Chemistry Letters
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DOI
Department
School of Biomedical Sciences
Remarks

NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters [20, 19, 2010] DOI 10.1016/j.bmcl.2010.07.140