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Thursday, October 02, 2014
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Development of High Throughput Assays for the Screening of Reversible and Mechanism-Based Cytochrome P450 Inhibition by Test Compounds
H. Gill, C. Dilworth, R. Southall, L. Shaw, L. Lemmers and D. Stangl

The prevalence and clinical implications, of mechanism-based CYP450 inhibition has placed greater emphasis on the early detection of compounds with this potential. We have developed and validated a high throughput reversible CYP450 inhibition assay using human liver microsomes and industry recommended probe substrates.

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Combination of in Vitro Caco-2 and Aqueous Solubility Screens with in Silico Physiological Modelling for the Prediction of Human Intestinal Absorption in Early Drug Discovery
S. Thomas, F.A. Brightman, H.J. Gill, B. Pufong and D.L. Cheney

With the increasing application of high-throughput assays for the determination of the in vitro ADME properties of compounds in lead identification and optimization, there is a growing need for efficient and cost-effective methods for interpreting theresulting data to enable well-informed selection to be made for compound progression.

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Applications of Laser Scanning Microplate Cytometry in High Content Screening
Paul Wylie, Christopher Lupton, Tristan Cope and Wayne Bowen

Traditional methods for High Content Analysis (HCA) use technologies such as flow cytometry and microscope-based imaging systems. Laser-scanning microplate cytometry has many advantages over these, and is more amenable for use in High Content Screening (HCS).

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Label-free Profiling of Ligands for Endogenous GPCRs Using a Cell-Based High Throughput Screening Technology
Ye Fang, Gary Li, and Ann M. Ferrie

The activation of GPCRs is known to lead to the dynamic translocation of multiple signaling molecules or molecular assemblies during its signaling cycle, and in many cases cytoskelatal reorganization. Such a movement and/or reorganization results in dynamic redistribution of cellular contents, equivalent to dynamic mass redistribution (DMR), which can be monitored online in living cells using Corning® Epic™ system – a label-free and non-invasive biosensor system.

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Utility of 405nm-Excitable Dyes in High Content Screening Using an Acumen Explorer Microplate Cytometer
Sarah Payne, Tristan Cope, Christopher Lupton, Jeffrey T. Hung and Paul Wylie

In this study, we have used an Acumen Explorer equipped with a violet 405nm laser in conjunction with a selection of shorter-wavelength amine-reactive fluorophores (Invitrogen, Molecular Probes) to demonstrate a greater utility for blue fluorescent probes within high content assays.

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TDS LIMS: A Platform for Comprehensive Management and Analysis of Screening Data
Karol Kozak, Marta Kozak, Jan Wagner, Hannes Grabner, Kerstin Korn, Eugenio Fava, Marit Biesold, Claudia Moebius, Anett Lohman and Ebrhard Krausz

Here we present a web-based bioinformatics solution for the management and analysis of all areas of cell-based screen experimentation: the Laboratory Information Management System of the Technology Development Studio (TDS-LIMS). TDS-LIMS is a software package consisting of the Library Checker, Library Browser, Scheduling Kit, Screen Browser and Screen Publisher.

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A High Content Primary Screening Assay Determining ERK and JNK Activation
Paul Wylie and Wayne Bowen

Here we present a rapid method for determining ERK and JNK activation, demonstrated using time course, concentration-dependence data and the effect of the MEK1/2 inhibitor UO126 on ERK activation obtained using the Acumen Explorer™ laser scanning cytometer analysing 384 well plates.

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Cell Cycle Analysis Using Microplate Cytometry: A Comparison of Laser and Dye Combinations
Tristan Cope, Christopher Lupton, Paul Wylie, Jeff Hung and Wayne Bowen

For improved screening capability, we have developed a cell cycle analysis method using an Acumen Explorer fluorescence microplate cytometer, capable of reading an entire 384 well microplate in about 10 minutes. The method can perform such analyses on fixed cells in situ, markedly simplifying sample preparation.

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Determination of Cell Colony Formation in a High Content Screening Assay
David Pole and Wayne Bowen

Here, laser scanning microplate cytometry has been used to provide an automated high content readout of the effects of cytostatic agents on colony formation. This approach determines colony number through the application of a spherical volume algorithm. This permits the differentiation of cytostatic effects where the number of colonies and size remains constant and cytotoxic effects where the size and number may be reduced.

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Scientific News
UW-Madison Team Developing ‘Tissue Chip’ to Screen Neurological Toxins
A faster, more affordable way to screen for neural toxins.
Promise for Treatment of Pancreatic Cancer
Ultrasound microbubbles can improve tumor absorption of cancer drugs.
Animal Testing can Mislead Drug Discovery and Development
Several blockbuster drugs would not be on the market, if scientists had relied solely on drug-uptake in animal trials, according to new research.
Marijuana Compound May Offer Treatment for AD
Extremely low levels of the compound in marijuana known as delta-9-tetrahydrocannabinol, or THC, may slow or halt the progression of Alzheimer’s disease.
New Advances in the Pre-clinical Evaluation of Hepatitis B Therapies
Imperial College London to present first public HBV Data from CN Bio in vitro liver model.
ADME of Antibody-Maytansinoid Conjugates
Continued understanding of the ADME properties of ADCs entering clinical evaluations should provide additional insight into attributes that may be necessary for clinical success.
Epigenetic Regulation of ADME-Related Genes
The promise of epigenetic research is its potential to identify additional sources of inter individual variability in drug disposition and response.
NIST Instrument Enables High-speed Chemical Imaging of Tissues
Researchers have demonstrated a dramatically improved technique for analyzing biological cells and tissues based on characteristic molecular vibration "signatures."
Finding Could Revolutionize Drug Discovery
A study by researchers at IRB Barcelona reveals the existence of information highways that connect and correlate distant sites within a single protein.
Researchers Develop ‘Onion’ Vesicles for Drug Delivery
University of Pennsylvania researchers have shown that dendrimer-based vesicles self-assemble with concentric layers of membranes, much like an onion.
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