Bioseek has taken a systems biology approach to pharma research by using drugs to agitate cells in over 20 different complex biological systems. The data generated is used to compile 'BioMaps' - drug profiles where the effect of each drug is screened through different systems. The cells in each system can be used to study cancer, metabolic disorders, inflammation, respiratory and cardiovascular diseases.

Instead of drug developers looking at the effect of a compound on a single target or even a set of related targets (such as kinases), there is an increasing tendency to study potential drugs across a variety of target types. Although this approach is more complicated, if successful, it enables scientists to see a fuller picture of how a drug interacts with the body, in terms of drug efficacy, mechanism, side-effects and which disease the drug is best suited for.

"Our goal is to be able to predict clinical activities in drug discovery," said Dr Ellen Berg, Bioseek's chief scientific officer, who was speaking at the Society for Biomolecular Sciences (SBS) conference in Montreal last week.

In doing so, Bioseek believes drugs developed utilising the tool would have a much higher chance of clinical success, reducing the amount of money spent in development - something bound to delight pharma companies as research costs soar.

This is difficult for several reasons, she explained. Firstly, the target for each drug has functions in multiple biological processes and any feedback mechanisms are hard to detect. Also, drugs can have effects on other parts of the body. As Berg clarified, this can cause dangerous side-effects which may only be detected once the drug is approved.

Before a profile can be made, Bioseek had to set up each system. Each system uses combinations of endothelial cells, blood leukocytes, macrophages, Th2-type T cells, bronchial epithelial cells, mast cells, smooth muscle cells, fibroblasts, and keratinocytes, according to the company.

Primary cells are used because "signalling pathways in cell lines become isolated, whereas primary cells retain feedback loops. This keeps all regulatory pathways intact," said Berg.

Then the effects of a drug on each system are examined. Which systems are activated or inhibited gives insights into a compound's mechanism and also which diseases it could be used to treat. The profiles can then be clustered together and used as a lead discovery tool, said Bioseek founder, Dr Eugene Butcher.

The same profiles can then be searched for compounds with similar mechanisms.

"We can quickly zero in and link chemistry and biology," said Butcher. Bioseek has its own internal drug discovery pipeline. As an example of using BioMap, Butcher explained that the company were looking to in-license a compound.

He said: "People didn't know the mechanism though, so we profiled and matched the compound. We saw that the target had known side-effect problems and so didn't license it."

With another if its internal programmes, Bioseek used the profiles to recognise that an investigational compound had unwanted effects on kinase proteins. Armed with this information, they were able to modify the compound such that the unwanted activity was removed, while the relevant drug effects were retained.

Berg also highlighted other advantages the approach holds over single target research. She explained that if you stimulate TNF-alpha, levels of the protein VCAM are increased. This relationship is easily observed in isolation. However, Bioseek has shown that if you look at multiple cytokines (IFN-gamma and IL-1 beta as well as TNF-alpha), VCAM levels don't change even if cytokine concentrations differ by over 100 times. This is because different pathways adapt to compensate for different levels of individual cytokines.

Berg also revealed that the company is currently working on a project to make some results available via a publicly accessible database. She also said: "Bioseek is expanding its coverage of biology to other diseases, especially in light of stem cell advances [which makes more cell types available]."

Although the tool could technically be used for personalised medicine, Berg said the company has not looked into this.

"It is the systems biology approach of embracing complexity," said Butcher.

"Most drug discoveries are descendants of drugs found through serendipity. We are now trying to engineer serendipity into the drug discovery process."