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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
Salford Lung Study - The First Real World Clinical Trial
In this podcast, we learn about the Salford Lung Study and its potential to revolutionize the way we assess new drugs and treatments around the world.
Nanoparticles Offer Promising Platform for Flavivirus Treatment
New nanoparticle effectively vaccinated mice against one dengue strain and could be created to target all four.
First Entirely 3D-printed Organ-on-a-Chip with Integrated Sensors
New approach to manufacturing may allow researchers to rapidly design organs-on-chips that match the properties of a specific disease or individual patient's cells.
Study Finds Key Regulator in Pulmonary Fibrosis
Researchers identify an enzyme that could open the way to therpies for chronic fatal lung disease.
Signaling Pathway Could Be Key to Improved Osteoporosis Treatment
Inhibition of SIK2 enzyme both stimulates bone formation and reduces bone breakdown in animal model.
Ovarian Cancer Insight
Study showed tumours release cytokines to attract macrophages, which secrete growth factors that in turn promote tumour growth.
Substance Can Potentially Postpone Aging
Researchers bridge the gap between two main aging theories - repairs to the DNA and poor functioning mitochondria.
Untangling Cause Of Memory Loss In Neurodegenerative Diseases
NIH-funded mouse study identifies a possible therapeutic target for a family of disorders.
New Model for Understanding Human Myeloma
Researchers develop mouse model where mice carry six human genes involved in human tumour growth.
Preventing Alzheimer's in Mice
Researchers have prevented the Alzheimer’s development in mice by using a virus delivery system to transport a specific gene into the brain.

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