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Turning the tables on drug discovery


EUREKA project E! 2314 O’SCREEN reverses the traditional screening process used to discover potentially active new pharmaceutical compounds. Testing single, targeted molecules rather than tens of thousands it promises vastly increased efficiency in drug discovery.

Until now, new molecules with the potential to be developed as drugs have been discovered by screening thousands of candidate new molecules and developing those showing potential activity in some therapeutic area. But the process is extremely expensive and wasteful. Now, a radical new option couples this unique approach with bioinformatics resources.

Reverse approach

Project coordinator Dr Jean-Yves Berthon from French pharmaceuticals company Greentech explains the way this ‘reverse approach’ developed. “We have a large database of 30,000 plants, with information on their botany, physiology, chemical components and their applications; also another database on 300,000 natural molecules coming from plants. We reasoned that if we had an idea of what molecules would have a particular pharmaceutical effect, we could find a natural source in our databases.” Greentech’s partner in the project was Drug Discovery Ltd, part of the natural products business of the Strathclyde Institute for Drug Research in Scotland, which has focused on identifying lead molecules from natural sources for drug development.

The method starts with knowledge of the key enzymes involved in particular diseases, such as acetylcholinesterase in the case of Alzheimer’s disease. Project team biochemists researched and identified what chemical entities (ligands) could be attached to the enzyme to alter its behaviour. They then consulted the databases of plant-derived molecules and plants to discover the natural sources of the ligands which could influence the enzyme. Identified in this way substances can then be extracted from the identified plant material and subjected to early-stage potentiality testing.

Fast and effective

Once potential compounds are confirmed, they can be supplied to pharmaceutical companies under licence in an easy-to-use condition, coated onto microplates ready for further studies and the development of the drug substance. Developing new drugs in this way is much faster than using conventional screening. It is also possible to reduce the side effects of conventionally-developed drugs - as the potential drug has been designed to achieve a particular change on the enzyme involved in the illness, and is less likely to interact with other systems.

The success generated by this EUREKA project has enabled Greentech to found Greenpharma, a new company entirely dedicated to pharmaceutical discovery. The future looks even brighter as Greentech itself has tripled its turnover by applying the technique to cosmetics and nutraceuticals.

Catherine Shiels | alfa
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