Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease (Q34543713)

2 August 2017

Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease (English)

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2 August 2017

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52

Dale Schenk

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Guriqbal S Basi

1

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Susanna Hemphill

2

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Elizabeth F Brigham

3

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Anna Liao

4

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Danielle L Aubele

5

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Jeanne Baker

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Robin Barbour

7

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Michael Bova

8

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Xiao-Hua Chen

9

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Michael S Dappen

10

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Tovah Eichenbaum

11

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2 August 2017

Erich Goldbach

12

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Jon Hawkinson

13

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Rose Lawler-Herbold

14

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2 August 2017

Kang Hu

15

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2 August 2017

Terence Hui

16

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Jacek J Jagodzinski

17

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Pamela S Keim

18

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Dora Kholodenko

19

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Lee H Latimer

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2 August 2017

Mike Lee

21

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Jennifer Marugg

22

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Matthew N Mattson

23

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Scott McCauley

24

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James L Miller

25

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Ruth Motter

26

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Linda Mutter

27

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2 August 2017

Martin L Neitzel

28

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2 August 2017

Huifang Ni

29

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Lan Nguyen

30

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Kevin Quinn

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Lany Ruslim

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Christopher M Semko

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Paul Shapiro

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Jenifer Smith

35

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Ferdie Soriano

36

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Balazs Szoke

37

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Kevin Tanaka

38

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Pearl Tang

39

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John A Tucker

40

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Xiacong Michael Ye

41

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2 August 2017

Mei Yu

42

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2 August 2017

Jing Wu

43

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2 August 2017

Ying-Zi Xu

44

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2 August 2017

Albert W Garofalo

45

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2 August 2017

John Michael Sauer

46

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Andrei W Konradi

47

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2 August 2017

Daniel Ness

48

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George Shopp

49

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Michael A Pleiss

50

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Stephen B Freedman

51

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2 August 2017

language of work or name

English

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publication date

29 December 2010

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Alzheimers Research & Therapy

2 August 2017

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2

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6

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36

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https://scigraph.springernature.com/pub.10.1186/alzrt60

2 August 2017

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Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease

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CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease.

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Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia

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Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease

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The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression

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Recent progress in the medicinal chemistry of gamma-secretase inhibitors

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Advances in gamma-secretase modulation.

7 July 2018

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N-(5-chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as gamma-secretase inhibitors.

7 July 2018

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Structure of the catalytic pore of gamma-secretase probed by the accessibility of substituted cysteines.

7 July 2018

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Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139.

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Gamma-secretase as a therapeutic target for the treatment of Alzheimer's disease.

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gamma-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site

7 July 2018

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Direct regulation of intestinal fate by Notch

7 July 2018

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Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells

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Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios.

7 July 2018

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Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation

7 July 2018

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Detergent-dependent dissociation of active gamma-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex

7 July 2018

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Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation

7 July 2018

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Gleevec inhibits β-amyloid production but not Notch cleavage

7 July 2018

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Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor

7 July 2018

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NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo

7 July 2018

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Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity

7 July 2018

1 reference

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Familial Alzheimer disease-linked presenilin 1 variants enhance production of both Abeta 1-40 and Abeta 1-42 peptides that are only partially sensitive to a potent aspartyl protease transition state inhibitor of "gamma-secretase".

7 July 2018

1 reference

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Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium

7 July 2018

1 reference

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Alzheimer's disease is a synaptic failure

7 July 2018

1 reference

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The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics

7 July 2018

1 reference

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Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity

7 July 2018

1 reference

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Requirement of Math1 for secretory cell lineage commitment in the mouse intestine

7 July 2018

1 reference

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Notch and presenilin: a proteolytic mechanism emerges

7 July 2018

1 reference

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Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease

7 July 2018

1 reference

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Aspartate mutations in presenilin and gamma-secretase inhibitors both impair notch1 proteolysis and nuclear translocation with relative preservation of notch1 signaling

7 July 2018

1 reference

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A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE

7 July 2018

1 reference

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Control of endodermal endocrine development by Hes-1

7 July 2018

1 reference

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Purification and cloning of amyloid precursor protein beta-secretase from human brain

7 July 2018

1 reference

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Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse

7 July 2018

1 reference

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Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease

7 July 2018

1 reference

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Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2

7 July 2018

1 reference

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Alzheimer's disease: a central role for amyloid

7 July 2018

1 reference

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Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein

7 July 2018

1 reference

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Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production

7 July 2018

1 reference

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Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors.

7 July 2018

1 reference

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Discovery of sulfonamide-pyrazole gamma-secretase inhibitors

27 October 2018

1 reference

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N-Bridged bicyclic sulfonamides as inhibitors of gamma-secretase.

27 October 2018

1 reference

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Design, synthesis, and structure-activity relationship of novel orally efficacious pyrazole/sulfonamide based dihydroquinoline gamma-secretase inhibitors

27 October 2018

1 reference

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Synthesis and structure-activity relationship of a novel series of heterocyclic sulfonamide gamma-secretase inhibitors.

27 October 2018

1 reference

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Novel orally bioavailable gamma-secretase inhibitors with excellent in vivo activity.

27 October 2018

1 reference

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What we have learned from the Myriad trials

27 October 2018

1 reference

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(S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing gamma-secretase inhibitor

27 October 2018

1 reference

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Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease

27 October 2018

1 reference

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Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibition

27 October 2018

1 reference

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Discovery of a novel series of Notch-sparing gamma-secretase inhibitors.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Transmembrane domain 9 of presenilin determines the dynamic conformation of the catalytic site of gamma-secretase

27 October 2018

1 reference

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Identification of gamma-secretase inhibitor potency determinants on presenilin

27 October 2018

1 reference

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Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice.

27 October 2018

1 reference

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Discovery of gamma-secretase inhibitors efficacious in a transgenic animal model of Alzheimer's disease.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

2,6-Disubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors.

27 October 2018

1 reference

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Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse.

27 October 2018

1 reference

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Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex.

27 October 2018

1 reference

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Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in the rat.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

4-substituted cyclohexyl sulfones as potent, orally active gamma-secretase inhibitors

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease.

27 October 2018

1 reference

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Cyclic sulfamide gamma-secretase inhibitors.

27 October 2018

1 reference

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Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Molecular-modeling based design, synthesis, and activity of substituted piperidines as gamma-secretase inhibitors.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Quantitative measurement of changes in amyloid-beta(40) in the rat brain and cerebrospinal fluid following treatment with the gamma-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}-secretase inhibitor

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Intracranially Administered Anti-Αβ Antibodies Reduce β-Amyloid Deposition by Mechanisms Both Independent of and Associated with Microglial Activation

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

The mechanism of gamma-secretase: multiple inhibitor binding sites for transition state analogs and small molecule inhibitors

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s).

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a gamma-secretase inhibitor: evidence for direct involvement of PS1 in the gamma-secretase cleavage complex.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway.

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide

27 October 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=3031881

Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors

27 October 2018

1 reference

PubMed

https://pubmed.ncbi.nlm.nih.gov/21190552

inferred from PubMed ID database lookup

12 December 2020

based on heuristic

Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitors

1 reference

PubMed

https://pubmed.ncbi.nlm.nih.gov/21190552

inferred from PubMed ID database lookup

12 December 2020

based on heuristic

A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1

1 reference

PubMed

https://pubmed.ncbi.nlm.nih.gov/21190552

inferred from PubMed ID database lookup

12 December 2020

based on heuristic

Identifiers

DOI

10.1186/ALZRT60

1 reference

Dimensions Publication ID

2 August 2017

0 references

1 reference

2 August 2017

1 reference