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Be Careful What You Ask for: Challenges of Predicting Human Clearance for a Low Metabolic Turnover Compound, ELND006
Kevin Quinn, David Nakamura, Heather Zhang, Shawn Gauby, Colin Lorentzen, Erich Goldbach, Amanda Moore, Salman Khetani, Earvin Liang, John-Michael Sauer and George Tonn,

A study of in vitro clearance of ELND006, a low turn-over compound.

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Global Gene Expression Changes Induced In Primary Human Hepatocytes By Thiazolidinediones Upon Repeat Dosing of HepatoPac™ Cultures
Michael McVay and Salman R. Khetani

An assessment of global gene expression changes in HepatoPac, a micropatterned co-culture of hepatocytes and stromal cells.

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A Long Term Culture Model for Primary Hepatocytes from Cynomolgus Monkeys
Simon Aoyama, Sara Lambirth, Chitra Kanchagar and Salman R. Khetani

The Macaca fascicularis or cynomolgus monkey is a non-human primate often used in pre-clinical animal studies. In this study, we applied microtechnology and tissue engineering techniques to cynomologus monkey hepatocytes in order to determine if these cells could be stabilized in micropatterned co-cultures similar to their human and rat counterparts.

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Live Cell Beating Assay Using Human iPSC-derived Cardiomyocytes for Evaluation of Drug Efficacy and Toxicity
Oksana Sirenko, Carole Crittenden, Blake Anson, Jayne Hesley, Yen-Wen Chen, Nick Callamaras and Evan F. Cromwell

A large percentage of new drugs fail in clinical studies due to cardiac toxicity. Development of highly predictive in vitro assays suitable for screening, safety assessment or other environments is therefore extremely important for drug development. Human cardiomyocytes derived from stem cell sources can greatly accelerate the discovery of cardiac drugs and improve drug safety by offering more clinically relevant cell-based models than those presently available.

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Quantification of cytokines on the SpectraMax® Paradigm® Multi-Mode Microplate Detection Platform using Alpha Technology
Caroline Cardonnel, Cathleen Salomo, Michael Katzlinger, Yvonne Fitzgerald, Cathy Olsen and Harald Hundsberger

Inflammation is accompanied by increased endothelial chemokine production and adhesion molecule expression, which may result in an extensive neutrophil infiltration. As such, the search for novel anti-inflammatory substances able to downregulate these parameters, as well as tissue damage, holds therapeutic promise.

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GALAS Modeling Methodology Applications In The Prediction Of Drug Metabolism Related Properties
Remigijus Didziapetris, Justas Dapkunas, Andrius Sazonovas and Pranas Japertas

Analytical identification of metabolites for a drug candidate is usually a time consuming and low-throughput task and is performed only at the later phases of drug development. Therefore the possibility to predict possible sites of human liver microsomal (HLM) metabolism using in silico techniques would be a very attractive feature for any medicinal chemist.

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Effective Use of In-Silico Tools in Lead Optimization
Pranas Japertas, Andrius Sazonovas and Kiril Lanevskij

Of all the challenges facing medicinal chemists in general, one of the most significant must be transforming an active molecule into a viable drug. Lead optimization efforts are guided by a combination of factors, such as potency, ease of synthesis, patentability concerns, specific synthetic constrains of the interaction with the target, as well as the lead’s toxicity and ADME properties.

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A Weight-of-Evidence Approach to Prioritisation based on Consensus across Multiple Sources of Information
Roman Affentranger (1), Barry Hardy (1), Glenn Myatt (2), Nina Jeliazkova (3), Matthew Clark (4), Jeffrey Wiseman (4)

We present the results of initial work carried out within the OpenToxLink Virtual Organization, applying a Weight-of-Evidence (WoE) approach based on consensus across multiple sources of information for the prediction of adverse effects of a large set of potential antimalarial compounds. The work was carried out as part of the EU FP7 project SYNERGY, evaluating the support of decision dashboards and event-driven collaborative research of software developed within SYNERGY.

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Three-dimensional quantitative structure-activity relationship analysis and ADME predictions of guanylhydrazone coactivator binding inhibitors of estrogen receptors
Sergey Shityakov, Thomas Dandekar

The estrogen receptors (ER) refer to a group of the nuclear hormone receptor superfamily of ligand-mediated transcriptional factors. Over expression of this type of receptors leads to a breast cancer progression. Hormone-responsive breast cancer develops resistance to conventional anti-cancer therapy, and this becomes a major problem in a breast cancer therapy.

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Scientific News
Bacteria Cooperate to Repair Damaged Siblings
New research unearths the unique ability of a certain type of soil borne bacteria to repair nearby damaged cells.
Vitamin E Keeps Muscles Healthy
Body builders have it right: vitamin E does help build strong muscles, and scientists appear to have figured out one important way it does it.
Microchip Captures Clusters of Circulating Tumor Cells
Researchers have developed a microfluidic chip that can capture rare clusters of circulating tumor cells, which could yield important new insights into how cancer spreads.
New Method For Measuring The Concentration Of Medicines In The Blood
Researchers at EPFL have come up with a quick and portable new device for measuring the amount of medicinal drugs in blood.
Label-Free Binding Analysis Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
Alternate Administration Routes for Psychotropic Drugs Reviewed
A review in the Annals of Pharmacotherapy has examined the literature on alternative routes of administration for antipsychotic and antidepressant medications.
Promising Results of Phase 1/2 Trial of Rociletinib in EGFR Lung Cancer Published
Results have been published of a multi-center phase I/II study of the investigational anti-cancer agent rociletinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC) that had progressed after previous treatment with EGFR inhibitors.
Epilepsy Drug Metabolism Test Launched for Epilepsy and Seizure Disorders
Courtagen Life Sciences, Inc have announced the release of a NGS test focused on detection of anti-epileptic drug (AED) compatibilities and interactions for patients receiving treatment for epilepsy or other seizure disorders.
Supercooling May Aid Drug Delivery
A new study published is the first to break down the rules governing the complex process of crystallization through rapid-cooling.
Quotient Clinical Completes Innovative First-In-Human Program
First-in-human clinical program designed to develop an optimal oral formulation.
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