| http://purl.uniprot.org/citations/23681056 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23681056 | http://www.w3.org/2000/01/rdf-schema#comment | "Proteolytic cleavage of amyloid precursor protein by β-secretase (BACE1) is a key step in generating the N-terminal of β-amyloid (Aβ), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer's disease. Inhibitors of BACE1 can reduce the levels of Aβ and thus have a therapeutic potential for treating the disease. We report here the identification of a series of small molecules bearing an indole acylguanidine core structure as potent BACE1 inhibitors. The initial weak fragment was discovered by virtual screening, and followed with a hit-to-lead optimization. With the aid of co-crystal structures of two discovered inhibitors (compounds 19 and 25) with BACE1, we explored the SAR around the indole and aryl groups, and obtained several BACE1 inhibitors about 1,000-fold more potent than the initial fragment hit. Accompanying the lead optimization, a previously under-explored sub-site opposite the flap loop was redefined as a potential binding site for later BACE1 inhibitor design."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.org/dc/terms/identifier | "doi:10.3390/molecules18055706"xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Chen T."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Ma L."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Shen J."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Xu Y."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Xiong B."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/author | "Zou Y."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/name | "Molecules"xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/pages | "5706-5722"xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/title | "Virtual screening and structure-based discovery of indole acylguanidines as potent beta-secretase (BACE1) inhibitors."xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://purl.uniprot.org/core/volume | "18"xsd:string |
| http://purl.uniprot.org/citations/23681056 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23681056 |
| http://purl.uniprot.org/citations/23681056 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23681056 |
| http://purl.uniprot.org/uniprot/#_P56817-mappedCitation-23681056 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23681056 |
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| http://purl.uniprot.org/uniprot/#_B7Z3Z4-mappedCitation-23681056 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23681056 |
| http://purl.uniprot.org/uniprot/#_B3KQJ4-mappedCitation-23681056 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23681056 |
| http://purl.uniprot.org/uniprot/#_Q76KP0-mappedCitation-23681056 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23681056 |