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Figure 1 Overview of DILI-sim A. Schematic overview of the key biological processes represented in DILI-sim B. Overview of different modules within DILI-sim. Each module is itself a model that captures a specific area of relevant biology, pharmacology and metabolism. This modular approach to DILI-sim allows the overall model to be built in manageable, testable pieces C. Knowledge management aspects of DILI-sim. Under each of the models, the supporting evidence is explicitly captured and hence the model acts as a highly structured knowledge repository
Figure 1 Overview of DILI-sim A. Schematic overview of the key biological processes represented in DILI-sim B. Overview of different modules within DILI-sim. Each module is itself a model that captures a specific area of relevant biology, pharmacology and metabolism. This modular approach to DILI-sim allows the overall model to be built in manageable, testable pieces C. Knowledge management aspects of DILI-sim. Under each of the models, the supporting evidence is explicitly captured and hence the model acts as a highly structured knowledge repository

Applying systems biology and computer simulations to predicting idiosyncratic DILI

19 August 2010 | By David Cook, Associate Director, Global Safety Assessment, AstraZeneca

Idiosyncratic drug-induced liver injury (DILI) is a rare adverse drug reaction which accounts for a significant amount of patient suffering, including death. Currently, idiosyncratic DILI is unpredictable and as a result arises late in the drug development process or even post-marketing. The prediction of idiosyncratic DILI based on preclinical or…

Figure 1 ASSET™ plan and detail Copyright: The Automation Partnership
Figure 1 ASSET™ plan and detail Copyright: The Automation Partnership

High content cell based primary screening for oncology targets – a perspective

25 June 2010 | By Peter Alcock, Colin Bath, Carolyn Blackett & Peter B. Simpson, Screening & Assay Sciences, Cancer Bioscience, AstraZeneca Alderley Park

Over the last 15 years, vendors have offered microscope-based instruments capable of producing images of fluorescent labelled components of cells grown in microtitre plates. These instruments are typically bundled with analysis software capable of defining the relative distribution of several fluorescent markers on a cell by cell basis1,2. As the…

Article 3: The implementation of rapid microbiological methods
Article 3: The implementation of rapid microbiological methods

Article 3: The implementation of rapid microbiological methods

24 June 2010 | By Michael J. Miller, Ph.D., President, Microbiology Consultants, LLC

This is the third in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. Rapid microbiological methods (RMMs) have been implemented by a number of companies around the world. In some cases, it is necessary to work with regulatory authorities in order…

Figure 1 Evolutionary systems biology for personalized medications. Over time, iterative cycles of experimentation and modelling facilitate a move from current understanding and therapeutic options, towards a more complete understanding of disease, with the possibility for personalised therapies. Inputs are needed in the form of system-wide data sets, which are highly anticipated to become increasingly detailed and accurate as analytical technologies improve. Interim benefits are also gained with each advancing cycle, in the form of continually evolving models that improve disease management and guide therapy (Figure produced with Jennifer Logan, University of Liverpool)
Figure 1 Evolutionary systems biology for personalized medications. Over time, iterative cycles of experimentation and modelling facilitate a move from current understanding and therapeutic options, towards a more complete understanding of disease, with the possibility for personalised therapies. Inputs are needed in the form of system-wide data sets, which are highly anticipated to become increasingly detailed and accurate as analytical technologies improve. Interim benefits are also gained with each advancing cycle, in the form of continually evolving models that improve disease management and guide therapy (Figure produced with Jennifer Logan, University of Liverpool)

High-throughput PCR based diagnostics: Linking sample handling to molecular oncology risk groups

24 June 2010 | By Ehsan G. Karimiani, Stephan Mohr & Philip J. R. Day, University of Manchester

Cancer molecular pathology broadly relies on the comparison between diseased and normal tissues, with statistically validated differences revealing cancerassociated pathways. This approach, although comparatively one-dimensional, has been remarkably successful, enabling identification of many types of malignant biomarkers and providing the means to develop pharmaceutical agents directed against pertinent biological targets.…

Drug Discovery and Development
Drug Discovery and Development

Novel medicines development for cancer treatment

24 June 2010 | By Hans Winkler, Global Head Oncology & Biomarker Programs, Ortho Biotech Oncology Research & Development, Johnson & Johnson

The pharmaceutical industry has reached a critical phase in its evolution. The cost and time to develop novel medicines has become unsustainable3. Reasons for this may include a much higher demand on evidence of safety and efficacy, rapidly increasing costs of contract research and the tremendous pressure on pricing and…

Figure 1 Targeting viral-associated RNAs at different stages of infection. Step 1, targeting of incoming RNA; step 2, targeting of viral mRNAs following provial integration; and step 3, targeting viral outgoing pregenomic template DNA.
Figure 1 Targeting viral-associated RNAs at different stages of infection. Step 1, targeting of incoming RNA; step 2, targeting of viral mRNAs following provial integration; and step 3, targeting viral outgoing pregenomic template DNA.

RNAi-based therapies for the treatment of HIV

24 June 2010 | By Marc S. Weinberg and Fiona van den Berg, Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of Witwatersrand

Since the discovery of RNA interference (RNAi) in 1998 and the demonstration of RNAi in mammalian cells in 2001, research into the mechanisms and applications of this pathway has moved swiftly. RNAi is capable of mediating potent and specific silencing of genes and has therefore shown promise in the development…

Automation in the Pharmaceutical Industry
Automation in the Pharmaceutical Industry

Trends in laboratory automation: From speed and simplicity to flexibility and information content

24 June 2010 | By Fernando A. Ramon Olayo, Manager, GlaxoSmithKline

The pharmaceutical industry has significantly influenced laboratory automation trends in the past two decades. The need to screen large collections of chemical entities in a short time with minimised consumption of reagents has driven a strong demand of parallelisation, automation, simplification and miniaturisation solutions from the suppliers of instruments, labware…

Figure 1 Cell undergoing senescence. Cell showing characteristics of cellular senescence: binucleated and flat and enlarged morphology
Figure 1 Cell undergoing senescence. Cell showing characteristics of cellular senescence: binucleated and flat and enlarged morphology

Cellular senescence as an anti-tumour mechanism

24 June 2010 | By Amancio Carnero, Scientist, Seville Biomedical Research Institute (IBIS/HUVR), Spanish National Research Council

One of the critical steps in human carcinogenesis is cellular immortalisation, a process in which cells must escape senescence and acquire an infinite lifespan. In the absence of immortalisation, although a cell might undergo malignant transformation, it could not proliferate indefinitely. Furthermore, it has been clearly established in vitro and…

Figure 1 MD simulation model of the opsin-transducin complex in a POPC lipid bilayer. Opsin and transducin are drawn in ribbon format and post-translational modification on opsin and transducin are represented in space-fill style. Opsin is oriented in the bilayer such that helix 4 (H4) is perpendicular to the plane of the bilayer. The extracellular surface is oriented toward the top of the figure.
Figure 1 MD simulation model of the opsin-transducin complex in a POPC lipid bilayer. Opsin and transducin are drawn in ribbon format and post-translational modification on opsin and transducin are represented in space-fill style. Opsin is oriented in the bilayer such that helix 4 (H4) is perpendicular to the plane of the bilayer. The extracellular surface is oriented toward the top of the figure.

Examining receptor activation: New technologies reveal how G protein-coupled receptors recognise ligands and talk to intracellular partners

24 June 2010 | By Thomas P. Sakmar, Laboratory of Molecular Biology & Biochemistry, Rockefeller University

Heptahelical G protein-coupled receptors (GPCRs) are arguably the most important single class of pharmaceutical drug targets in the human genome. According to Overington, of the 266 human targets for approved drugs, a remarkable 27 per cent correspond to rhodopsin-like, or Family A, GPCRs. Despite recent dramatic advances in targeting of…

Figure 3
Figure 3

Raman spectroscopy for the analysis of drug products and drug manufacturing processes

9 May 2010 | By Prof. Thomas De Beer, Assistant-Professor, Process Analytical Technology, Faculty of Pharmaceutical Sciences, University of Ghent

This article aims at supplying a concise overview on the application of Raman spectroscopic analysis methods within the pharmaceutical drug product manufacturing world. Firstly, there will be a focus on the rapid and nondestructive off-line analysis feasibility of Raman spectroscopy for final drug products. Herewith, several possible sources of error…

qPCR: Current technologies and future applications
qPCR: Current technologies and future applications

qPCR: Current technologies and future applications

9 May 2010 | By European Pharmaceutical Review

A diverse and widely applicable laboratory technique, qPCR is vital for the progression of drug discovery, enabling detection and quantification and commonly used for both diagnostic and basic research. This roundtable brings together experts from a wide range of pharmaceutical applications to discuss current technologies and future applications of qPCR…

Implementing chemometrics in late stage development and manufacturing
Implementing chemometrics in late stage development and manufacturing

Article 2: The implementation of rapid microbiological methods

9 May 2010 | By Michael J. Miller, Ph.D., President, Microbiology Consultants, LLC

This is the second in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. Method validation is the process used to confirm that an analytical procedure employed for a specific test is reliable, reproducible and suitable for its intended purpose. All analytical…

Finding novel targets for anticancer target discovery

9 May 2010 | By Wolfgang Link, Experimental Therapeutics Program, Centro Nacional de Investigaciones Oncologicas (CNIO)

Advances in our understanding of the molecular basis of cancer together with novel approaches to interfere with signal transduction pathways have opened new horizons for anticancer target discovery. In particular, the image based large scale analysis of cellular phenotypes that arise from genetic or chemical perturbations paved the way for…

SBS Biopharmaceuticals Symposium: Exploring synergies across drug formats

9 May 2010 | By EPR

Biopharmaceuticals is a rapidly growing sector of the pharmaceutical industry. Major pharmaceutical companies have recognised this trend in recent years and defined ambitious targets for the proportion of their pipeline that is expected to be filled by novel biopharmaceuticals. It is inevitable that many of the scientists involved with small-molecule…

drug discovery & drug development
drug discovery & drug development

Implementation of appropriate assays and HTS technologies in drug discovery

9 May 2010 | By Sheraz Gul, Vice President, European ScreeningPort GmbH

In this article, an overview regarding advances in assay formats for specific target classes and options that should be considered when considering hardware will be given. There has been a significant growth in the assay and automation technologies that are available for compound screening activities and it is essential to…