Issue 1 2006

HTS using siRNA libraries

Issue 1 2006 / 2 February 2006 / Quan Du, Institute of Molecular Medicine, Peking University, Meihong Chen, Chinese Human Genome Center Beijing, Claes Wahlestedt, Scripps Florida and Zicai Liang, Karolinska Institute

Although synthetic siRNA libraries are becoming more available, most high throughput siRNA library-based screening was carried out with siRNA libraries encoded by different vectors. In this article, siRNA library construction methods and HTS applications are summarised.

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Tagged with: Claes Wahlestedt, Functional genomics, HTS (High Throughput Screening), Karolinska Institute, Meihong Chen, Peking University, Quan Du, Zicai Liang

Connecting HCS to CNS drug targets

Issue 1 2006 / 2 February 2006 / Carmel B. Nanthakumar, Senior Research Scientist – Automated Imaging and Electrophysiology, Neuroscience Research Centre, Merck Sharp and Dohme

HCS has been implemented as a key technology to address complex biology associated with CNS drug targets. This review will describe a new generation of HCS assays including multiplexed HCS assays with biochemical markers, novel techniques for studying receptor internalisation and the application of HCS to neural network cultures that have facilitated CNS drug discovery.

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Tagged with: Carmel B. Nanthakumar, HCS (High Content Screening), Merck Sharp and Dohme

In vitro and in vivo techniques in CNS drug discovery

Issue 1 2006 / 2 February 2006 / Vahri Beaumont, Magnus Ivarsson and Keith A. Wafford, The Neuroscience Research Centre, Merck Sharp and Dohme, UK

In spite of an increased understanding of brain mechanisms in recent years, there has been a lack of major new drugs being registered for psychiatric and neurological conditions1,2. To prioritise drug discovery resources and provide early proof-of-concept studies for novel compounds and mechanisms, the pharmaceutical industry is increasingly focusing on trying to identify and develop early biological markers (biomarkers).

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Tagged with: Electrophysiology, Keith A. Wafford, Magnus Ivarsson, Merck Sharp and Dohme, Vahri Beaumont

The HUPO Brain Proteome Project

Issue 1 2006 / 2 February 2006 / Kai A. Reidegeld, Michael Hamacher, Helmut E. Meyer, Christian Stephan; MPC, Medical Proteom-Center, Ruhr-University of Bochum, Martin Blüggel, Gerhard Körting, Daniel Chamrad, Christian Scheer; Protagen AG, Herbert Thiele; Bruker Daltonik GmbH, Chris Taylor, Michael Müller, Rolf Apweiler, Philip Jones; EBI, European Bioinformatics Institute, Lennart Martens; Department of Medical Protein Research, Ghent University

The proteome analysis started by the Human Proteome Organization (HUPO)1 is the second big international consortium project after the sequencing of the human genome by the Human Genome Project (HUGO)2. The aim of the HUPO Brain Proteome Project (BPP)3 is to derive in depth knowledge of the brain from analysing samples with state-of-the-art proteomics techniques.

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Tagged with: Bruker Daltonik GmbH, Chris Taylor, Christian Scheer, Christian Stephan, Daniel Chamrad, European Bioinformatics Institute (EBI), Gerhard Körting, Ghent University, Helmut E. Meyer, Herbert Thiele, Kai A. Reidegeld, Lennart Martens, Martin Blüggel, Michael Hamacher, Michael Müller, Philip Jones, Protagen AG, Proteomics, Rolf Apweiler, Ruhr-University of Bochum

Cost, knowledge and convenience: facing the facts

Issue 1 2006 / 2 February 2006 / Professor David Littlejohn, Head of the Department of Pure and Applied Chemistry at the University of Strathclyde, Director of CPACT at the University of Strathclyde

There can be no doubt that the FDA’s initiative on Process Analytical Technologies (PAT) has had an enormous impact on the pharmaceutical industries. However, the emergence of ’born again‘ PAT devotees in pharma companies has caused mild amusement in other industries where on-line analysis has been an integral part of (more…)

Tagged with: David Littlejohn, PAT, University of Strathclyde

Setting new standards in Ultra HTS

Issue 1 2006 / 2 February 2006 / Elisabeth Pook, Stefan Martin Mundt, Adrian Tersteegen, Department of Cardiovascular Research, Pharma Research Center Wuppertal, Bayer HealthCare AG

Ultra high-throughput screening (UHTS) offers the possibility to discover novel pharmacophores. To benefit from UHTS special demands concerning assay quality and data analysis have to be met.

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Tagged with: Adrian Tersteegen, Bayer HealthCare, Elisabeth Pook, HTS (High Throughput Screening), Stefan Martin Mundt

In vitro safety pharmacology profiling

Issue 1 2006 / 2 February 2006 / Jacques Hamon, Kamal Azzaoui, Steven Whitebread, Laszlo Urban, Edgar Jacoby, Bernard Faller, Novartis Institutes for BioMedical Research

One major cause of the late failure of drugs in development (i.e. attrition) is the lack of clinical safety of the compounds (accounting for approximately 30% of failures together with toxicology)1. One of the key elements is the off-target effects of the compounds, causing adverse drug reaction (ADRs).

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Tagged with: Bernard Faller, Drug Safety, Edgar Jacoby, Jacques Hamon, Kamal Azzaoui, Laszlo Urban, Novartis Institutes for BioMedical Research, Steven Whitebread

Opportunities for Rapid Microbial Methods

Issue 1 2006 / 2 February 2006 / Anthony M. Cundell, Ph.D. Consulting Microbiologist

Since the 2000 publication of the PDA Technical Report Number 33 Testing Methods, rapid microbial methods (RMM) have not lived up to their promise for changing routine Quality Control microbiological testing in the pharmaceutical industry. With the next generation of rapid microbial methods emerging from the R&D laboratories of instrument manufacturers, this article will discuss the obstacles to the successful implementation of the currently marketed technologies and strategies to overcome these obstacles.

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Tagged with: Anthony M. Cundell, Consulting Microbiologist, Microbiology

Making the lab workhorse run faster

Issue 1 2006 / 2 February 2006 / Holly Hilton, Ph.D. and Charu Kanwal Ph.D. Research Informatics, Genetics and Genomics Hoffmann La-Roche Inc.

Quantitative real-time PCR, the workhorse of any genomics lab, is a well established technique that has numerous uses due to its simplicity and flexibility. In this article we will review a brief history of real time PCR, discuss our strategy for optimising a lab running Quantitative-RT-PCR and describe how this technique fits into the drug discovery process. We will conclude with some on-going issues regarding RT-PCR data generation and analysis.

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Tagged with: Charu Kanwal, Hoffmann La-Roche Inc., Holly Hilton, PCR

Tool for candidate drug selection

Issue 1 2006 / 2 February 2006 / Anders Grahnén, Ph.D.,Professor of Clinical Drug Development Sciences, Uppsala University; Chief Scientific Officer, Quintiles Nordic Region

Utilising man as a species for candidate drug selection is per se not a new concept, but the development of new technologies have made it possible to be realised in practice.

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Tagged with: Anders Grahnén, Microdosing, Quintiles Nordic Region, Uppsala University