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Co-operation through certification

24 March 2006 | By Bengt Ljungqvist, Ph.D. and Berit Reinmüller, Ph.D. KTH Stockholm

To verify that cleanroom and clean zones are adequately installed and functioning they are usually validated during three occupancy states. First, when the installation is complete with all services connected and functioning, as-built; secondly during at-rest conditions when equipment is installed and running in a manner agreed upon by customer…

HTS using siRNA libraries

2 February 2006 | By 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.

Connecting HCS to CNS drug targets

2 February 2006 | By 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…

In vitro and in vivo techniques in CNS drug discovery

2 February 2006 | By 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…

The HUPO Brain Proteome Project

2 February 2006 | By 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…

Cost, knowledge and convenience: facing the facts

2 February 2006 | By 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…

Setting new standards in Ultra HTS

2 February 2006 | By 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.

In vitro safety pharmacology profiling

2 February 2006 | By 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).

Opportunities for Rapid Microbial Methods

2 February 2006 | By 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…

Making the lab workhorse run faster

2 February 2006 | By 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…

Tool for candidate drug selection

2 February 2006 | By 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.

Applications in target ID and validation

11 November 2005 | By Oliver C. Steinbach, Head of Department, Technology Management, ALTANA Pharma AG

RNAi technology provides the ‘loss of function’ approach, which has been widely used in the last couple of years for analysis of gene function, and in drug discovery for identification and validation of potential drug target candidates. This technology is now widely applied for functional screens in order to identify…

Meeting the challenge with a new facility

11 November 2005 | By EPR

The conclusion of the Genome Sequencing Project – far from providing the solution to the problem of human disease – has created further questions that had not previously been considered. Hence, the age of genomics has initiated the need to examine the body’s real biochemical actors: proteins, to learn about…

Options for quantitative analysis by real-time PCR

11 November 2005 | By Gareth Elvidge, PhD, Genomics Group, Wellcome Trust Centre for Human Genetics, University of Oxford

The expansion of microarray-based gene expression studies has led to an increase in demand for gene-specific PCR-based methods for independent validation of results. Although a number of technologies are available to meet this requirement the most popular is currently real-time PCR.

A new approach to ion channel hit identification

11 November 2005 | By Martin J. Main, Karen Jones, Biological Chemistry, AstraZeneca R&D, UK, Mats A. Svensson, Dirk Weigelt and Markus Haeberlein, Chemistry, AstraZeneca R&D, Sweden

Advances in assay technology are driving an exciting new era in ion channel drug discovery. Here, we present a case study describing the use of computational chemistry and focussed library screening to drive rapid hit identification.

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