Results 201 to 210 of about 25,969 (247)

Mechanism of gamma‐secretase modulators

Alzheimer's & Dementia, 2022
AbstractBackgroundAmyloid‐beta (Aβ) peptides are believed to be integral to Alzheimer’s disease (AD) pathogenesis through their role in the “amyloid hypothesis,” in which the accumulation of Aβ peptides initiates a cascade of pathological events leading to neurodegeneration and AD.
Joanna E. Luo, Steven L Wagner, Yueming Li   +2 more
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Anilinotriazoles as potent gamma secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2014
The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.
Adriana I, Velter, François P, Bischoff, Didier, Berthelot, Michel, De Cleyn, Daniel, Oehlrich, Libuse, Jaroskova, Gregor, Macdonald, Garrett, Minne, Serge, Pieters, Frederik, Rombouts, Sven, Van Brandt, Yves, Van Roosbroeck, Michel, Surkyn, Andrés A, Trabanco, Gary, Tresadern, Tongfei, Wu, Herman, Borghys, Marc, Mercken, Chantal, Masungi, Harrie, Gijsen   +19 more
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Piperidine-derived γ-secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2010
This Letter details the SAR of a novel series of piperidine-derived gamma-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Abeta42, increase Abeta38 and have no effect on Abeta40 levels.
Adrian, Hall, Richard L, Elliott, Gerard M P, Giblin, Ishrut, Hussain, James, Musgrave, Alan, Naylor, Rosemary, Sasse, Beverley, Smith   +7 more
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Cyclic sulfamide γ-secretase inhibitors

Bioorganic & Medicinal Chemistry Letters, 2005
A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo gamma-secretase activity.
Tim, Sparey, Dirk, Beher, Jonathan, Best, Mirlinda, Biba, José L, Castro, Earl, Clarke, Joanne, Hannam, Timothy, Harrison, Huw, Lewis, Andrew, Madin, Mark, Shearman, Bindi, Sohal, Nancy, Tsou, Christopher, Welch, Jonathan, Wrigley   +14 more
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Gamma-secretase inhibition.

Biochemical Society transactions, 2003
Development of Alzheimer's disease (AD) pathology appears to be causally related to age-dependent changes in the metabolism of the amyloid-beta peptide (A beta), leading to its enhanced aggregation and deposition. gamma-Secretase is a crucial enzyme for the generation of A beta from the amyloid-beta precursor protein and thus represents a valid ...
D, Beher, M S, Shearman
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Iminoheterocycles as γ-secretase modulators

Bioorganic & Medicinal Chemistry Letters, 2010
The synthesis of a novel series of iminoheterocycles and their structure-activity relationship (SAR) as modulators of gamma-secretase activity will be detailed. Encouraging SAR generated from a monocyclic core led to a structurally unique bicyclic core.
John P, Caldwell, Chad E, Bennett, Troy M, McCracken, Robert D, Mazzola, Thomas, Bara, Alexei, Buevich, Duane A, Burnett, Inhou, Chu, Mary, Cohen-Williams, Hubert, Josein, Lynn, Hyde, Julie, Lee, Brian, McKittrick, Lixin, Song, Giuseppe, Terracina, Johannes, Voigt, Lili, Zhang, Zhaoning, Zhu   +17 more
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Relationship between presenilinase and gamma-secretase

Drug News & Perspectives, 2003
Genetic and neuropathological studies suggest that processing of amyloid precursor protein (APP) to yield amyloid beta-protein (Abeta) plays an important role in the pathogenesis of Alzheimer's disease (AD). One of the current therapeutic efforts for AD is directed towards blocking the gamma-secretase activity that produces Abeta.
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γ-Secretase: Substrates and Inhibitors

Molecular Neurobiology, 2002
The amyloid beta-protein (Abeta) deposited in Alzheimer's disease (AD), the most common form of dementia in the elderly, is a secreted proteolytic product of the amyloid beta-protein precursor (APP). Generation of Abeta from the APP requires two sequential proteolytic events, beta-secretase cleavage to generate the amino terminus, followed by gamma ...
Marjorie J, Rochette, M Paul, Murphy
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Reconstitution of γ-secretase activity

Nature Cell Biology, 2003
gamma-Secretase is a membrane protein complex with an unusual aspartyl protease activity that catalyses the regulated intramembranous cleavage of the beta-amyloid precursor protein (APP) to release the Alzheimer's disease (AD)-associated amyloid beta-peptide (Abeta) and the APP intracellular domain (AICD).
Dieter, Edbauer, Edith, Winkler, Joerg T, Regula, Brigitte, Pesold, Harald, Steiner, Christian, Haass   +5 more
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Uncovering gamma-secretase.

Current Alzheimer research, 2005
Accumulation of the amyloid beta-peptide (Abeta) in the brain is believed to initiate a series of neurotoxic events that causes neurodegeneration in Alzheimer's disease (AD). Abeta is generated by processing of the beta-amyloid precursor protein (APP) through the successive action of two proteolytic enzymes, beta-secretase and gamma-secretase.
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