Real-Time Parallel Analysis
Also at the meeting was Chip-Man Technologies (www.chipmantech.com), a technology company launching Cell-IQ, a long-awaited tool for drug discovery and other applications that allows real time parallel analysis of all morphological and physiological changes down to the individual cell level in continuous cell culture.
In Cell-IQ, All-in-Focus optics, incubation, environmental conditions, detection, and analysis are all controlled by an integrated artificial intelligence system; this allows monitoring and measurement of all changes, such as size, shape, migration, dendritic outgrowth, apoptosis, or proliferation, without resorting to tags or labels.
Multiple events can be monitored in parallel from each microplate well and the information generated outputted in a simple graphical form. Stored image files can be repeatedly interrogated to retrieve new data, thus eliminating the need to repeat experimentation.
Cell-IQ is optimized for measuring cell lines, co-cultures, primary cells, and stem cells. "Cell-IQ is a wet lab in a complete package," explained Jula Korpinen, CEO of Chip-Man.
"Cell-IQ contains the incubator, detector, in silico expert analysts, and technicians." The company, which was founded in 2002 from the University of Tampere, the Technical Research Center of Finland, and other Finnish academic institutions, has just raised first-round private funding of x1.2 million to further develop the Cell-IQ system.
The product will help meet the growing need for automated cell-based assays for drug discovery and development, entering a market currently estimated at $500 million and growing at 30% per annum.
Case histories presented at the conference showed how strategies and technologies are put into practice. Pfizer (www.pfizer.com) has been developing CCR5 antagonists against HIV/AIDS, an area where there is an ongoing need for effective agents.
A lesion in the CCR5 gene has been linked to lack of progression of the disease in high-risk groups, highlighting this as a new target. Tony Wood, Ph.D., head of discovery chemistry at Pfizer, described the evolution of a compound now in Phase III and the work that had been done on moderating lipophilicity, potency, and toxicity of the compound.
"We set high targets in terms of delivering selectivity against ion channels linked with cardiac toxicity," he said. The lead compound has already been shown to reduce viral load with its antiviral effect lasting beyond the last day of dosing. It may have some limitations but has been shown to be first in class, according to Dr. Wood.
Alison Holt, M.D., senior medical advisor at AstraZeneca (www.astrazeneca.com), described the development of fulvestrant, a drug for advanced breast cancer. Fulvestrant is an antiestrogen based on estrodiol, which is meant to lack the adverse effects on the endometrium of tamoxifen.
The drug has been shown to be similar in efficacy to tamoxifen but so far has not demonstrated superiority over the more traditional drug, despite promising preclinical data. "We need to do more work to understand patient populations," said Dr. Holt.
Professor Ulf Eriksson, Ph.D., principal scientist at AstraZeneca R&D in Sweden, described the development of ximelagtran, an oral anticoagulant.
Standard treatment of clotting disorders with warfarin is fraught with difficulties, and there is a clear need for new approaches. Ximelagtran is an inhibitor of thrombin, a key component of the clotting cascade.
"If there is a good understanding of the biology and the target it helps toward the goal," said Dr. Eriksson. Ximelagatran is actually a pro-drug of the compound that was first discovered, melagratran, which has good pharmacodynamics but not good pharmacokinetics. Ximelagatran has better properties and also has a low potential for drug-drug interactions.