New drug screening technique to benefit pharma
process of drug compound screening promises a increased efficiency
in drug discovery whilst keeping costs down to a minimum.
The new method aims to improve on current techniques, which take new molecules that have been discovered by screening thousands of candidate new molecules and developing those that show potential activity in some therapeutic area.
In the majority of large pharma companies, high-throughput screening has become the industry standard.
The primary objective is to screen the largest number of compounds available in order to have the best chance of identifying chemistries that are able to modulate the target.
The compounds are often poorly characterised, so selection of the leads is based primarily on efficacy. The most efficacious compounds are then serially evaluated to characterise their specificity and bio-availability and to minimise their toxicity and drug: drug interactions.
This bottom-up approach to lead identification and subsequent optimisation is slow, expensive and fundamentally flawed - the most efficacious compound will not necessarily provide you with the best drug.
EUREKA project E2314 O'SCREEN reverses this traditional screening process by testing single, targeted molecules rather than tens of thousands it promises vastly increased efficiency in drug discovery.
The method starts with knowledge of the key enzymes involved in particular diseases, such as acetylcholinesterase in the case of Alzheimer's disease.
Scentists 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.
"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," said project coordinator Jean-Yves Berthon from French pharmaceuticals company Greentech.
"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."
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 EUREKA Initiative aims to strengthen European competitiveness by promoting cross-border, market-oriented, collaborative R&D. It enables industry and research institutes from 35 member countries and the EU to collaborate in a bottom-up approach to developing and exploiting innovative technologies.
Since 1985, substantial public and private funding has been deployed through EUREKA, an intergovernmental network to support leading edge R&D.More information about EUREKA may be found >here.
