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Merck Sharp and Dohme - Articles and news items

Figure 1 High content screening analysis of HepG2 cells stained under control (A,C,E,G), or 24 (B,D,F) and 72 (H) h incubations with 10-6 / 10-5 M doxorubicin with different fluorescent probes, i.e.. Hoechst 33342, Fluo-4, TOTO-3 and TMRM

High Content Screening for in vitro toxicity testing

Issue 3 2011, Screening / 20 June 2011 / Willem G.E.J. Schoonen, Walter M.A. Westerink, Femke M. van de Water and G. Jean Horbach, Department of Toxicology & Drug Disposition, Merck Sharp & Dohme

The application of High Content Screening for in vitro toxicity testing is a relatively new approach in the preclinical research phase of drug development. A battery of tests have been developed for screening on general parameters such as cytotoxicity, while more dedicated assays are available with respect to the identification of genotoxicity, phospholipidosis, steatosis and cholestasis. All these tests are very beneficial within the pharmaceutical industry for the selection of appropriate candidates for drug development as well as for reduction of the attrition rate.

High content screening (HCS) is quickly growing in popularity within the field of in vitro toxicity testing. The maturity of HCS equipment and software has made HCS accessible for many technicians and scientists working in the area of cellular and molecular biology. Although this technique was introduced in the mid 1990’s, the simplification in the use of the software programs, the growth in computer storage capacities as well as the improved qualities of resolution of the digital microscopic cameras has largely increased the accessibility of this equipment. At the start of HCS technology, many scientists were sceptical about this technique as image-based mathematical algorithms had to be written for the analysis.

Connecting HCS to CNS drug targets

Issue 1 2006, Past issues / 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.

In vitro and in vivo techniques in CNS drug discovery

Issue 1 2006, Past issues / 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).

Getting a handle on neuronal behaviour in culture

Issue 2 2005, Past issues / 20 May 2005 / Peter B. Simpson, Senior Research Fellow – Automated imaging, Neuroscience Research Centre, Merck Sharp and Dohme

In drug discovery for CNS diseases, the use of complex neural cell culture systems offers many advantages. Innovations in high content screening enable us to identify compounds which affect key cell biological properties in such cultures. We can bridge the divide between kinetic and endpoint screening by use of another novel technology, RNAi.


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