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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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New Approach for In Silico Genotoxicity Testing of Impurities and Degradants
Kiril Lanevskij, Liutauras Juska, Remigijus Didziapetris and Pranas Japertas

This study presents a novel approach to aid this assessment based on probabilistic predictors of mutagenicity in Ames test and binding to Estrogen Receptor, supplemented by a knowledge-based system of structural alerts.

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In silico Identification of Metabolic Soft Spots: Case Study Using ACD/ADME Suite Software
Justas Dapkunas, Andrius Sazonovas, Remigijus Didziapetris and Pranas Japertas

Metabolic stability, determined in liver microsomes, is one of the primary assays used in early drug discovery. A key factor limiting compound half-life is the cytochrome P450 mediated metabolism. High clearance by these enzymes implies a higher and more frequent dosing as well as poses a risk for individual variations in exposure.

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Scientific News
Retractable Protein Nanoneedles
The ability to control the transfer of molecules through cellular membranes is an important function in synthetic biology; a new study from researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) introduces a novel mechanical method for controlling release of molecules inside cells.
Iron in the Blood Could Cause Cell Damage
Concentrations of iron similar to those delivered through standard treatments can trigger DNA damage within 10 minutes, when given to cells in the laboratory.
Advancing Synthetic Biology
Living systems rely on a dizzying variety of chemical reactions essential to development and survival. Most of these involve a specialized class of protein molecules — the enzymes.
Insights into the Function of the Main Class of Drug Targets
About thirty percent of all medical drugs such as beta-blockers or antidepressants interact with certain types of cell surface proteins called G protein coupled receptors.
Honey’s Potential to Save Lives
The healing powers of honey have been known for thousands of years.
Muscles on-a-Chip
This study may help explain why stem cell-based therapies have so far shown limited benefits for heart attack patients in clinical trials.
3-D Printed Lifelike Liver Tissue for Drug Screening
A team led by engineers at the University of California, San Diego has 3D-printed a tissue that closely mimics the human liver's sophisticated structure and function. The new model could be used for patient-specific drug screening and disease modeling.
Envigo Rat Models Proven to be Susceptible to Intra-Vaginal HSV-2 Infection and Protectable
Scientific findings establish the effectiveness of new approach to investigate the protective effects of vaccine candidates and anti-viral microbodies and to study asymptomatic primary genital HSV-2 infection.
Valvena, GSK Sign New R&D Collaboration
Valneva to supply process development services for EB66® -based Influenza vaccines.
Food Triggers Creation of Regulatory T Cells
IBS researchers document how normal diet establishes immune tolerance conditions in the small intestine.
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