Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening
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 methylthiazoletetr...
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| Format: | Journal Article |
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Pergamon
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/9340 |
| _version_ | 1848745921116897280 |
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| author | Xu, W. Chen, G. Zhu, W. Zuo, Zhili |
| author_facet | Xu, W. Chen, G. Zhu, W. Zuo, Zhili |
| author_sort | Xu, W. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:25:02Z |
| format | Journal Article |
| id | curtin-20.500.11937-9340 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:25:02Z |
| publishDate | 2010 |
| publisher | Pergamon |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-93402019-02-19T04:27:47Z Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening Xu, W. Chen, G. Zhu, W. Zuo, Zhili FRET Virtual screening Bioassay BACE-1 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/9340 10.1016/j.bmcl.2010.07.140 Pergamon fulltext |
| spellingShingle | FRET Virtual screening Bioassay BACE-1 Xu, W. Chen, G. Zhu, W. Zuo, Zhili Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title | Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title_full | Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title_fullStr | Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title_full_unstemmed | Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title_short | Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| title_sort | identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening |
| topic | FRET Virtual screening Bioassay BACE-1 |
| url | http://hdl.handle.net/20.500.11937/9340 |