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Development of High-Throughput PAMPA as an In Vitro Model of Passive Transcellular Permeation
Helen Gill, Boris Pufong, Peter Dykstra, Lynn Lemmers and Darwin Cheney

The absorption of orally administered compounds is largely determined by their ability to cross the gastrointestinal tract. Cell culture models can be intensive and limited to a narrow pH range. Assays using artificial membranes, such as PAMPA (parallel artificial membrane permeation assay) can be used as an alternative approach to assess in vitro transcellular passive permeation.

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A Strategy to Investigate Potential Pro-Arrhythmic Effects of Compounds During the Drug Discovery and Development Process
Clemens Möller, Anja Nordheim, Heike Deisemann, Irene Schlobohm, Rainer Netzer, and Andreas Scheel

For pharmaceutical companies it is not only essential to identify HERG interacting compounds early during the drug discovery and development process, but also to understand potential effects of compounds on the cardiac action potential. This helps to increase the safety for patients, and to avoid the costs of unsuccessful projects in later phases.

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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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Scientific News
Molecular Event Mapping Opens Door to more in silico Tests
It is hoped that this new approach to mapping and predicting the impact of chemical compounds in the body could reduce the need for toxicity tests in animals.
Protein-engineered Cages Aid Studies of Cell Functions
The Cages, from researchers at Tokyo Institute of Technology, to deliver an important signalling molecule, carbon monoxide, into cells.
Wallet-Sized Labs The Next Big Thing
RMIT researchers are developing inexpensive, portable toxicology laboratories so small you could fit them in your wallet.
Altered Milk Protein Can Deliver AIDS Drug to Infants
Binding with an antiretroviral drug promises to greatly improve treatment for infants and young children suffering from HIV/AIDS.
New Drug for Common Liver Disease Improves Liver Health
An experimental drug aimed at treating a common liver disease showed promising results and potential problems in a multicenter clinical trial funded by the NIH.
Immunotherapy for Cancer Toxic with Obesity
UC Davis researchers link increased body fat and lethal drug reactions in mice.
An Unlikely Use for Diamonds
Tiny diamonds provide new possibilities for accurate measurements of processes inside living cells with potential to improve drug delivery and cancer therapeutics.
Microscopic “Walkers” Find Their Way Across Cell Surfaces
Technology could provide a way to deliver probes or drugs to cell structures without outside guidance.
Revalesio’s Drug Shows Promise in Treating Alzheimer’s
Multiple published research studies outline the potential for RNS60 to effectively treat Alzheimer’s disease by protecting neuronal function and restoring neuronal plasticity.
Getting Metabolism Right
Analysis of 89 models of metabolic processes finds flaws in 44 of them — but suggests corrections.
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