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Analytical techniques

 

The increasing role of toxicology in early decision making processes
The increasing role of toxicology in early decision making processes
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The increasing role of toxicology in early decision making processes

19 April 2011 | By Eckhard von Keutz, Senior Vice President, Head Global Early Development, Bayer HealthCare

Clinical development costs are rising at an alarming rate. There is a decreasing success rate for new drug candidate approval and the duration of development is increasing. In other words, industry is spending more and getting less from current drug development efforts. In 2010, 21 new drugs were approved in…

Figure 1The autophagy pathway. Autophagy proceeds in three steps: initiation by protein kinase complexes
Figure 1The autophagy pathway. Autophagy proceeds in three steps: initiation by protein kinase complexes
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Molecular drug targets in autophagy

19 April 2011 | By Robin Ketteler, MRC LMCB, University College London

Autophagy is a cellular stress response to diverse stimuli such as starvation, infection and DNA damage. Autophagy plays important roles in the progression of various diseases including cancer, neurodegenerative diseases and Crohn’s disease. Despite recent advances in our understanding of the autophagy machinery, surprisingly little effort has been undertaken towards…

Figure 1 High Content Imaging Technology. The leading fluorescent high content imaging platforms established within the pharmaceutical and biotechnology industry. Represented are; A. Fully automated high throughput high content imaging systems (ImageXpress, InCell, BD Pathway, ScanR, Opera and the Arrayscan). B. Live cell kinetic imaging systems (IncuCyteFLR and Cell-IQ) and C. Fluorescent tissue slide imaging platform (Scanscope FL)
Figure 1 High Content Imaging Technology. The leading fluorescent high content imaging platforms established within the pharmaceutical and biotechnology industry. Represented are; A. Fully automated high throughput high content imaging systems (ImageXpress, InCell, BD Pathway, ScanR, Opera and the Arrayscan). B. Live cell kinetic imaging systems (IncuCyteFLR and Cell-IQ) and C. Fluorescent tissue slide imaging platform (Scanscope FL)
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Advancing high content analysis towards improving clinical efficacy

16 February 2011 | By Neil Carragher, Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh

High-content analysis is primed to play a prominent role in a new era of drug discovery research that places greater emphasis on clinical translation at all stages of the discovery process from target identification to proof-of-concept testing. High content analysis provides a technical bridge between reductionist targetdirected drug discovery approaches…

Figure 1 Typical critical path for small molecule Drug Discovery programs. Drug Discovery involves identification of a Target of interest for which an assay is developed. This assay is then adapted for screening purposes and utilised in a High Throughput Screening campaign against small molecule libraries. The High Throughput Screening campaign will usually yield many Hit molecules. Confirmation, Counter and Selectivity Screening will provide a final list of Validated Hits.
Figure 1 Typical critical path for small molecule Drug Discovery programs. Drug Discovery involves identification of a Target of interest for which an assay is developed. This assay is then adapted for screening purposes and utilised in a High Throughput Screening campaign against small molecule libraries. The High Throughput Screening campaign will usually yield many Hit molecules. Confirmation, Counter and Selectivity Screening will provide a final list of Validated Hits.
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Establishing assays and small molecule screening facilities for Drug discovery programs

16 February 2011 | By Sheraz Gul, Vice President & Head of Biology, European ScreeningPort GmbH

Although many of the marketed small molecule drugs have been discovered by research and development efforts within the pharmaceutical industry, there has been a paradigm shift with external sources increasingly being relied upon to fill their pipelines. This trend is likely to increase and the key pre-clinical activities carried out…

Figure 1 Baseline treated Raman spectra of Zirtek 10 milligram tablet (blue) and titanium dioxide (red) measured using the Ahura Truscan instrument
Figure 1 Baseline treated Raman spectra of Zirtek 10 milligram tablet (blue) and titanium dioxide (red) measured using the Ahura Truscan instrument
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Authentication of medicines using Raman spectroscopy

16 February 2011 | By Sulaf Assi, University of Hertfordshire, and Robert Watt & Tony Moffat, The School of Pharmacy, University of London

Raman spectroscopy offers a rapid and non-destructive technique for the identification of counterfeit medicines. Handheld Raman instruments offer the advantages of carrying the laboratory to the sample and giving a rapid pass or fail answer for the medicine inspected. It can identify a medicine regardless of its physical form as…

Figure 1 A: Control B: Docetaxel treated Induction of apoptosis with Docetaxel compared to untreated. The lower right quadrant represents cells in early apoptosis and cells in the upper right quadrant are cells in late apoptosis due to PI entering the cells through leaky membranes. C: Control D: Docetaxel treated Cell cycle of control cells and Docetaxel treated cells. The first peak shows cells in G0/G1 and the second peak is cells in G2/M. The breast cancer cell line, MDA MB231, was treated with 10nM docetaxel or DMSO control for 72 hours. Cells were harvested, the nuclei isolated and stained with PI. Samples were run on the LSR II flow cytometer and analyed in FCS Express software. Docetaxel arrests the cells in G2/M
Figure 1 A: Control B: Docetaxel treated Induction of apoptosis with Docetaxel compared to untreated. The lower right quadrant represents cells in early apoptosis and cells in the upper right quadrant are cells in late apoptosis due to PI entering the cells through leaky membranes. C: Control D: Docetaxel treated Cell cycle of control cells and Docetaxel treated cells. The first peak shows cells in G0/G1 and the second peak is cells in G2/M. The breast cancer cell line, MDA MB231, was treated with 10nM docetaxel or DMSO control for 72 hours. Cells were harvested, the nuclei isolated and stained with PI. Samples were run on the LSR II flow cytometer and analyed in FCS Express software. Docetaxel arrests the cells in G2/M
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Application of flow cytometry in drug discovery

16 December 2010 | By Dana Buckman, Senior Scientist, Biomarkers – Translational Research, Pfizer

Flow cytometry can be used to advance our understanding of diseases in multiple ways. Drug effects and dosages can be ascertained in vitro, along with patient selection based on mutations and antigen profiles. Within the Diagnostic Biomarkers group of Translational Research at Pfizer, we are utilising flow cytometry in conjunction…

Figure 1 Schematic illustration of the recombinant antibody microarray set-up
Figure 1 Schematic illustration of the recombinant antibody microarray set-up
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Developing and applying recombinant antibody microarrays for high-throughput disease proteomics

16 December 2010 | By Carl A.K. Borrebaeck and Christer Wingren, Department of Immunotechnology and CREATE Health, Lund University

Deciphering crude proteomes in the quest for candidate biomarker signatures for disease diagnostics, prognostics and classifications has proven to be challenging using conventional proteomic technologies. In this context, affinity protein microarrays, and in particular recombinant antibody microarrays, have recently been established as a promising approach within high-throughput (disease) proteomics1-3. The…

Thermo Fisher Scientific logo with background
Thermo Fisher Scientific logo with background
news

Thermo Fisher Scientific Launches Mass Frontier 7.0

10 November 2010 | By

Thermo Fisher Scientific Inc., the world leader in serving science, today announced Mass Frontier 7.0, the newest release of its small molecule structural elucidation software. The software simplifies the management, evaluation and interpretation of mass spectral data and can be used for metabolism, metabolomics, forensics, natural products, impurities and degradants…

Figure 2 Spray drying. Screenshot of on-line PSD analysis, providing real-time PSD-measurement (top-right) and continuous PSD-monitoring (bottom; d50-orange, d90-blue, d10-green, transmission-red)
Figure 2 Spray drying. Screenshot of on-line PSD analysis, providing real-time PSD-measurement (top-right) and continuous PSD-monitoring (bottom; d50-orange, d90-blue, d10-green, transmission-red)
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Applying PAT in pharmaceutical processes

1 November 2010 | By Mario Hellings, Tom Van den Kerkhof, Jeroen Geens and Steve Mehrman, Johnson & Johnson

As cited by the FDA, “Process Analytical Technology (PAT) is a system for designing, analysing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.”1 The main goal of PAT…

Figure 1 Principle of 2D cell migration assays. (A) A confluent monolayer of cells is mechanically wounded (‘scratch assay’), usually with a sterile pipette tip, leaving two wound edges (dashed lines) separated by a void. Cells at the leading edges quickly assume a polarised morphology and form broad lamellae pointing into the direction of the void. Over time, cells migrate into the void and, eventually, completely close the wound (B). Cell migration is qualitatively assessed by visual inspection and can be quantitated by measuring gap width or by enumeration of cells populating the wound. Images show T98G human glioblastoma cells immediately after wounding (A) or after 24 hours of migration (B). Distance between lines is one millimetre
Figure 1 Principle of 2D cell migration assays. (A) A confluent monolayer of cells is mechanically wounded (‘scratch assay’), usually with a sterile pipette tip, leaving two wound edges (dashed lines) separated by a void. Cells at the leading edges quickly assume a polarised morphology and form broad lamellae pointing into the direction of the void. Over time, cells migrate into the void and, eventually, completely close the wound (B). Cell migration is qualitatively assessed by visual inspection and can be quantitated by measuring gap width or by enumeration of cells populating the wound. Images show T98G human glioblastoma cells immediately after wounding (A) or after 24 hours of migration (B). Distance between lines is one millimetre
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Advances in two-dimensional cell migration assay technologies

1 November 2010 | By Andreas Vogt, Department of Pharmacology and Chemical Biology and the University of Pittsburgh Drug Discovery Institute, University of Pittsburgh

Cell motility plays an important role in many human diseases and normal cellular processes. Cell migration is critical for wound healing as cells of the inflammatory system and fibroblasts populate the wound and initiate re-epithelialisation1. On the other hand, unregulated cell migration contributes to cancer cell invasion and metastasis2. Agents…

Figure 1 Distribution of drugs in vivo depends on various equilibrium and rate processes between compartments
Figure 1 Distribution of drugs in vivo depends on various equilibrium and rate processes between compartments
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Bio-mimetic chromatography to predict drug distribution in vivo

29 October 2010 | By Klara Valko, Analytical Chemistry, GlaxoSmithKline Medicines Research Centre

A major concern for the pharmaceutical industry is the high attrition rate (>90 per cent) of potential drug molecules failing during late stages of the drug discovery process. This may be due to lack of efficacy in the clinic, unexpected side effects or unfavourable pharmacokinetics. There is a need for…

Figure 1 Schematic of workflow for MALDI MS imaging from slicing fresh tissue to image
Figure 1 Schematic of workflow for MALDI MS imaging from slicing fresh tissue to image
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MS-based clinical proteomics: biomarker discovery in men’s cancer

29 October 2010 | By Brian Flatley Dept of Chemistry, University of Reading, Reading and Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Peter Malone Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Rainer Cramer Dept of Chemistry, University of Reading, Reading

Each year, approximately 10,000 men in the UK die as a result of prostate cancer (PCa) making it the third most common cancer behind lung and breast cancer. Worldwide, more than 670,000 men are diagnosed every year with the disease. Current methods of diagnosis of PCa mainly rely on the…