Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 최선 | * |
dc.date.accessioned | 2018-11-30T16:30:11Z | - |
dc.date.available | 2018-11-30T16:30:11Z | - |
dc.date.issued | 2017 | * |
dc.identifier.issn | 0022-2623 | * |
dc.identifier.issn | 1520-4804 | * |
dc.identifier.other | OAK-23632 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247139 | - |
dc.description.abstract | Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of beta-amyloid peptides (pGlu-A beta) and thus may participate in the pathogenesis of Alzheimer's disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, A beta 3E-42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform A beta and total A beta and restored cognitive functions. This potent A beta-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong-interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD. | * |
dc.language | English | * |
dc.publisher | AMER CHEMICAL SOC | * |
dc.title | Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer's Agents Based on Rational Design | * |
dc.type | Article | * |
dc.relation.issue | 6 | * |
dc.relation.volume | 60 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 2573 | * |
dc.relation.lastpage | 2590 | * |
dc.relation.journaltitle | JOURNAL OF MEDICINAL CHEMISTRY | * |
dc.identifier.doi | 10.1021/acs.jmedchem.7b00098 | * |
dc.identifier.wosid | WOS:000397546000029 | * |
dc.identifier.scopusid | 2-s2.0-85016278636 | * |
dc.author.google | Van-Hai Hoang | * |
dc.author.google | Phuong-Thao Tran | * |
dc.author.google | Cui, Minghua | * |
dc.author.google | Ngo, Van T. H. | * |
dc.author.google | Ann, Jihyae | * |
dc.author.google | Park, Jongmi | * |
dc.author.google | Lee, Jiyoun | * |
dc.author.google | Choi, Kwanghyun | * |
dc.author.google | Cho, Hanyang | * |
dc.author.google | Kim, Hee | * |
dc.author.google | Ha, Hee-Jin | * |
dc.author.google | Hong, Hyun-Seok | * |
dc.author.google | Cho, Sun | * |
dc.author.google | Kim, Young-Ho | * |
dc.author.google | Lee, Jeewoo | * |
dc.contributor.scopusid | 최선(8659831000) | * |
dc.date.modifydate | 20240305081003 | * |