FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2584335005> ?p ?o ?g. }

• W2584335005 abstract "Alzheimer's disease (AD), the most common form of dementia, is the biggest unmet medical need in neurology due to the lack of disease–modifying therapies. Major research efforts are ongoing to find a disease–modifying AD agent targeting the putative AD pathogens Αβ40 and Αβ42 by blocking their synthesis from APP through the inhibition of either β–secretase or γ–secretase enzymes. The initial enthusiasm for γ–secretase inhibitors (GSIs) as potential disease–modifying AD agents was dampened by the subsequent discovery of other γ–secretase substrates, especially Notch, and the resulting concerns about selectivity and mechanism–based side effects (e.g., G.I. toxicity) due to inhibition of Notch processing. Thus, the development of an acceptable pharmaceutical agent would target the discovery of a GSI possessing minimal inhibition of Notch processing and maximal inhibition of APP processing to reduce Αβ40/42 levels. Utilizing HTS screening of the Wyeth and ArQule compound collections, we have identified the lead, 4–chloro–N–[(1S,2S)–1–(hydroxymethyl)–2–methylbutyl]–benzenesulfonamide, which not only inhibited γ–secretase cleavage of APP (EC50Αβ40 and Αβ42 = 2078 nM and 1938 nM, respectively) but also was sparing of Notch cleavage (EC50 = 20,000 nM). Structure–activity relationships in this new series and the discovery of more potent GSIs will be discussed." @default.
• W2584335005 created "2017-02-10" @default.
• W2584335005 creator A5006925784 @default.
• W2584335005 creator A5010672313 @default.
• W2584335005 creator A5015437792 @default.
• W2584335005 creator A5016214250 @default.
• W2584335005 creator A5016732315 @default.
• W2584335005 creator A5020330814 @default.
• W2584335005 creator A5022782879 @default.
• W2584335005 creator A5025543241 @default.
• W2584335005 creator A5032561810 @default.
• W2584335005 creator A5035490280 @default.
• W2584335005 creator A5040526199 @default.
• W2584335005 creator A5042402553 @default.
• W2584335005 creator A5045339813 @default.
• W2584335005 creator A5046234493 @default.
• W2584335005 creator A5051970415 @default.
• W2584335005 creator A5060384593 @default.
• W2584335005 creator A5060447576 @default.
• W2584335005 creator A5062487450 @default.
• W2584335005 creator A5065521904 @default.
• W2584335005 creator A5076903779 @default.
• W2584335005 creator A5078958470 @default.
• W2584335005 creator A5081382789 @default.
• W2584335005 creator A5086631386 @default.
• W2584335005 creator A5088980863 @default.
• W2584335005 creator A5089379836 @default.
• W2584335005 date "2006-07-01" @default.
• W2584335005 modified "2023-09-27" @default.
• W2584335005 title "P4-244: Discovery of a novel series of notch-sparing γ-secretase inhibitors" @default.
• W2584335005 doi "https://doi.org/10.1016/j.jalz.2006.05.1984" @default.
• W2584335005 hasPublicationYear "2006" @default.
• W2584335005 type Work @default.
• W2584335005 sameAs 2584335005 @default.
• W2584335005 citedByCount "0" @default.
• W2584335005 crossrefType "journal-article" @default.
• W2584335005 hasAuthorship W2584335005A5006925784 @default.
• W2584335005 hasAuthorship W2584335005A5010672313 @default.
• W2584335005 hasAuthorship W2584335005A5015437792 @default.
• W2584335005 hasAuthorship W2584335005A5016214250 @default.
• W2584335005 hasAuthorship W2584335005A5016732315 @default.
• W2584335005 hasAuthorship W2584335005A5020330814 @default.
• W2584335005 hasAuthorship W2584335005A5022782879 @default.
• W2584335005 hasAuthorship W2584335005A5025543241 @default.
• W2584335005 hasAuthorship W2584335005A5032561810 @default.
• W2584335005 hasAuthorship W2584335005A5035490280 @default.
• W2584335005 hasAuthorship W2584335005A5040526199 @default.
• W2584335005 hasAuthorship W2584335005A5042402553 @default.
• W2584335005 hasAuthorship W2584335005A5045339813 @default.
• W2584335005 hasAuthorship W2584335005A5046234493 @default.
• W2584335005 hasAuthorship W2584335005A5051970415 @default.
• W2584335005 hasAuthorship W2584335005A5060384593 @default.
• W2584335005 hasAuthorship W2584335005A5060447576 @default.
• W2584335005 hasAuthorship W2584335005A5062487450 @default.
• W2584335005 hasAuthorship W2584335005A5065521904 @default.
• W2584335005 hasAuthorship W2584335005A5076903779 @default.
• W2584335005 hasAuthorship W2584335005A5078958470 @default.
• W2584335005 hasAuthorship W2584335005A5081382789 @default.
• W2584335005 hasAuthorship W2584335005A5086631386 @default.
• W2584335005 hasAuthorship W2584335005A5088980863 @default.
• W2584335005 hasAuthorship W2584335005A5089379836 @default.
• W2584335005 hasConcept C126322002 @default.
• W2584335005 hasConcept C161879069 @default.
• W2584335005 hasConcept C185592680 @default.
• W2584335005 hasConcept C202751555 @default.
• W2584335005 hasConcept C2777752112 @default.
• W2584335005 hasConcept C2778171954 @default.
• W2584335005 hasConcept C2779134260 @default.
• W2584335005 hasConcept C2780591741 @default.
• W2584335005 hasConcept C31705614 @default.
• W2584335005 hasConcept C36103677 @default.
• W2584335005 hasConcept C502032728 @default.
• W2584335005 hasConcept C55493867 @default.
• W2584335005 hasConcept C62478195 @default.
• W2584335005 hasConcept C71240020 @default.
• W2584335005 hasConcept C71924100 @default.
• W2584335005 hasConcept C96529984 @default.
• W2584335005 hasConcept C98274493 @default.
• W2584335005 hasConceptScore W2584335005C126322002 @default.
• W2584335005 hasConceptScore W2584335005C161879069 @default.
• W2584335005 hasConceptScore W2584335005C185592680 @default.
• W2584335005 hasConceptScore W2584335005C202751555 @default.
• W2584335005 hasConceptScore W2584335005C2777752112 @default.
• W2584335005 hasConceptScore W2584335005C2778171954 @default.
• W2584335005 hasConceptScore W2584335005C2779134260 @default.
• W2584335005 hasConceptScore W2584335005C2780591741 @default.
• W2584335005 hasConceptScore W2584335005C31705614 @default.
• W2584335005 hasConceptScore W2584335005C36103677 @default.
• W2584335005 hasConceptScore W2584335005C502032728 @default.
• W2584335005 hasConceptScore W2584335005C55493867 @default.
• W2584335005 hasConceptScore W2584335005C62478195 @default.
• W2584335005 hasConceptScore W2584335005C71240020 @default.
• W2584335005 hasConceptScore W2584335005C71924100 @default.
• W2584335005 hasConceptScore W2584335005C96529984 @default.
• W2584335005 hasConceptScore W2584335005C98274493 @default.
• W2584335005 hasIssue "3S_Part_19" @default.
• W2584335005 hasLocation W25843350051 @default.
• W2584335005 hasOpenAccess W2584335005 @default.
• W2584335005 hasPrimaryLocation W25843350051 @default.
• W2584335005 hasRelatedWork W1991697476 @default.

• next