FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2014773623> ?p ?o ?g. }

• W2014773623 endingPage "713" @default.
• W2014773623 startingPage "702" @default.
• W2014773623 abstract "Alzheimer’s disease (AD) is characterized pathologically by an abundance of extracellular neuritic plaques composed primarily of the 42-amino acid amyloid β peptide variant (Aβ42). In the majority of familial AD (FAD) cases, e.g., those harboring mutations in presenilin 1 (PS1), there is a relative increase in the levels of Aβ42 compared to the levels of Aβ40. We previously reported the characterization of a series of aminothiazole-bridged aromates termed aryl aminothiazole γ-secretase modulators or AGSMs [Kounnas, M. Z., et al. (2010) Neuron 67, 769–780] and showed their potential for use in the treatment of FAD [Wagner, S. L., et al. (2012) Arch. Neurol. 69, 1255–1258]. Here we describe a series of GSMs with physicochemical properties improved compared to those of AGSMs. Specific heterocycle replacements of the phenyl rings in AGSMs provided potent molecules with improved aqueous solubilities. A number of these soluble γ-secretase modulators (SGSMs) potently lowered Aβ42 levels without inhibiting proteolysis of Notch or causing accumulation of amyloid precursor protein carboxy-terminal fragments, even at concentrations approximately 1000-fold greater than their IC50 values for reducing Aβ42 levels. The effects of one potent SGSM on Aβ peptide production were verified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, showing enhanced production of a number of carboxy-truncated Aβ species. This SGSM also inhibited Aβ42 peptide production in a highly purified reconstituted γ-secretase in vitro assay system and retained the ability to modulate γ-secretase-mediated proteolysis in a stably transfected cell culture model overexpressing a human PS1 mutation validating the potential for use in FAD." @default.
• W2014773623 created "2016-06-24" @default.
• W2014773623 creator A5000930248 @default.
• W2014773623 creator A5009879178 @default.
• W2014773623 creator A5010416927 @default.
• W2014773623 creator A5023581135 @default.
• W2014773623 creator A5025755515 @default.
• W2014773623 creator A5043158901 @default.
• W2014773623 creator A5050004777 @default.
• W2014773623 creator A5051193896 @default.
• W2014773623 creator A5067195047 @default.
• W2014773623 creator A5076252609 @default.
• W2014773623 creator A5078806051 @default.
• W2014773623 date "2014-01-22" @default.
• W2014773623 modified "2023-10-06" @default.
• W2014773623 title "Soluble γ-Secretase Modulators Selectively Inhibit the Production of the 42-Amino Acid Amyloid β Peptide Variant and Augment the Production of Multiple Carboxy-Truncated Amyloid β Species" @default.
• W2014773623 cites W1483703465 @default.
• W2014773623 cites W1572225000 @default.
• W2014773623 cites W1605886981 @default.
• W2014773623 cites W1861730929 @default.
• W2014773623 cites W1928655587 @default.
• W2014773623 cites W1964927015 @default.
• W2014773623 cites W1965013631 @default.
• W2014773623 cites W1973185157 @default.
• W2014773623 cites W1976804482 @default.
• W2014773623 cites W1980825524 @default.
• W2014773623 cites W1981293839 @default.
• W2014773623 cites W1982816514 @default.
• W2014773623 cites W1991435932 @default.
• W2014773623 cites W1992331666 @default.
• W2014773623 cites W2008041561 @default.
• W2014773623 cites W2010240177 @default.
• W2014773623 cites W2011347889 @default.
• W2014773623 cites W2016811754 @default.
• W2014773623 cites W2019567619 @default.
• W2014773623 cites W2019961788 @default.
• W2014773623 cites W2034102528 @default.
• W2014773623 cites W2043383967 @default.
• W2014773623 cites W2066621849 @default.
• W2014773623 cites W2068932168 @default.
• W2014773623 cites W2075829521 @default.
• W2014773623 cites W2081836725 @default.
• W2014773623 cites W2088989293 @default.
• W2014773623 cites W2104132043 @default.
• W2014773623 cites W2113690827 @default.
• W2014773623 cites W2131819352 @default.
• W2014773623 cites W2156217397 @default.
• W2014773623 cites W2157064933 @default.
• W2014773623 cites W2158854213 @default.
• W2014773623 cites W2168804449 @default.
• W2014773623 doi "https://doi.org/10.1021/bi401537v" @default.
• W2014773623 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3929337" @default.
• W2014773623 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24401146" @default.
• W2014773623 hasPublicationYear "2014" @default.
• W2014773623 type Work @default.
• W2014773623 sameAs 2014773623 @default.
• W2014773623 citedByCount "42" @default.
• W2014773623 countsByYear W20147736232014 @default.
• W2014773623 countsByYear W20147736232015 @default.
• W2014773623 countsByYear W20147736232016 @default.
• W2014773623 countsByYear W20147736232017 @default.
• W2014773623 countsByYear W20147736232018 @default.
• W2014773623 countsByYear W20147736232019 @default.
• W2014773623 countsByYear W20147736232020 @default.
• W2014773623 countsByYear W20147736232021 @default.
• W2014773623 countsByYear W20147736232022 @default.
• W2014773623 countsByYear W20147736232023 @default.
• W2014773623 crossrefType "journal-article" @default.
• W2014773623 hasAuthorship W2014773623A5000930248 @default.
• W2014773623 hasAuthorship W2014773623A5009879178 @default.
• W2014773623 hasAuthorship W2014773623A5010416927 @default.
• W2014773623 hasAuthorship W2014773623A5023581135 @default.
• W2014773623 hasAuthorship W2014773623A5025755515 @default.
• W2014773623 hasAuthorship W2014773623A5043158901 @default.
• W2014773623 hasAuthorship W2014773623A5050004777 @default.
• W2014773623 hasAuthorship W2014773623A5051193896 @default.
• W2014773623 hasAuthorship W2014773623A5067195047 @default.
• W2014773623 hasAuthorship W2014773623A5076252609 @default.
• W2014773623 hasAuthorship W2014773623A5078806051 @default.
• W2014773623 hasBestOaLocation W20147736231 @default.
• W2014773623 hasConcept C126322002 @default.
• W2014773623 hasConcept C153911025 @default.
• W2014773623 hasConcept C175344181 @default.
• W2014773623 hasConcept C179104552 @default.
• W2014773623 hasConcept C181199279 @default.
• W2014773623 hasConcept C185592680 @default.
• W2014773623 hasConcept C202751555 @default.
• W2014773623 hasConcept C2777633098 @default.
• W2014773623 hasConcept C2779134260 @default.
• W2014773623 hasConcept C2779281246 @default.
• W2014773623 hasConcept C2781307694 @default.
• W2014773623 hasConcept C31705614 @default.
• W2014773623 hasConcept C36103677 @default.
• W2014773623 hasConcept C502032728 @default.
• W2014773623 hasConcept C515207424 @default.
• W2014773623 hasConcept C55493867 @default.
• W2014773623 hasConcept C68026918 @default.
• W2014773623 hasConcept C71924100 @default.

• next