University of Pittsburgh - Articles and news items

Drug Discovery and Development

A new vision of drug discovery and development

Drug Discovery, Issue 6 2012 / 18 December 2012 / D. Lansing Taylor, Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation Professor of Computational and Systems Biology, University of Pittsburgh School of Medicine

The pharmaceutical industry has experienced a decade of turbulence driven by the ‘patent cliff’ as major revenue generators are lost to generic status, coupled to the absence of a sustainable pipeline of drug candidates in development that have a good chance of being approved and launched. It is generally agreed that the lowest hanging drug discovery ‘fruit’ has been harvested and the industry is addressing diseases that are more complex. The current one target, one drug discovery and development paradigm continues to exhibit more than 90 per cent attrition mainly due to the lack of success in translating preclinical efficacy and safety data into successful human trials. It has also become clear that efficient drug discovery and development requires a deeper understanding of the complexity of human biology early in the process. The high attrition rates increase the costs and with the science indicating that precision therapeutics will replace the blockbuster model, the challenge of drug discovery and development is even greater. The traditional business model of pharmaceutical companies working in silos is no longer sustainable…

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

Advances in two-dimensional cell migration assay technologies

Issue 5 2010, Screening / 1 November 2010 / 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 that affect cell motility, either positively or negatively, could therefore find applications as promoters of wound healing or as antimetastatic drugs. Cell migration in a biological context is an extremely complex process and the understanding of genetic and biochemical determinants remains incomplete.


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