ArticleAssay and drug development technologies2009
A miniaturized 1536-well format gamma-secretase assay.
Article in Assay and drug development technologies, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.bioRxiv : the preprint server for biology · 2024Article
- Brain Permeable Tafamidis Amide Analogs for Stabilizing TTR and Reducing APP Cleavage.ACS medicinal chemistry letters · 2020Article
- Substrate interaction inhibits γ-secretase production of amyloid-β peptides.Chemical communications (Cambridge, England) · 2020Article
- γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors.Frontiers in aging neuroscience · 2020Article
- Imaging and Functional Analysis of γ-Secretase and Substrate in a Proteolipobead System with an Activity-Based Probe.Analytical chemistry · 2016Article
- A novel high throughput 1536-well Notch1 γ -secretase AlphaLISA assay.Combinatorial chemistry & high throughput screening · 2013Article
- A class of allosteric caspase inhibitors identified by high-throughput screening.Molecular cell · 2012Article
- An image-based biosensor assay strategy to screen for modulators of the microRNA 21 biogenesis pathway.Combinatorial chemistry & high throughput screening · 2012Article
- A high throughput scintillation proximity imaging assay for protein methyltransferases.Combinatorial chemistry & high throughput screening · 2012Article
- A high-throughput scintillation proximity-based assay for human DNA ligase IV.Assay and drug development technologies · 2012Article
- Dual-fluorescence isogenic high-content screening for MUC16/CA125 selective agents.Molecular cancer therapeutics · 2011Article
- Dual role of alpha-secretase cleavage in the regulation of gamma-secretase activity for amyloid production.The Journal of biological chemistry · 2010Article
- High-content assay to identify inhibitors of dengue virus infection.Assay and drug development technologies · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
gamma-Secretase is an aspartyl protease that cleaves multiple substrates including the amyloid precursor protein (APP) and the Notch proteins. Abnormal proteolysis of APP is involved in the pathogenesis of Alzheimer's disease (AD) and overactive Notch signaling plays an oncogenic role in a variety of cancers. gamma-Secretase has emerged as a promising target for drug development in the treatment of AD and cancer. Assays with increased capacity for high-throughput screening would allow for quicker screening of chemical libraries and facilitate inhibitor development. We have developed a homogeneous time-resolved fluorescence (HTRF)-based assay that makes use of a novel biotinylated recombinant APP substrate and solubilized membrane preparation as the source of the gamma-secretase enzyme. The assay was miniaturized to a 1536-well format and validated in a pilot screen against a library of approximately 3,000 compounds. The overall assay performance was robust due to a calculated Z' factor of 0.74 and its demonstrated ability to identify known gamma-secretase inhibitors such as pepstatin A. This validated assay can readily be used for primary screening against large chemical libraries searching for novel inhibitors of gamma-secretase activity that may represent potential therapeutics for AD and a variety of neoplasms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.