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EMD's compound library contains around 600,000 compounds. Some of them are being sent to the consortium's central library in ScotlandStage Image

EMD's compound library contains around 600,000 compounds. Some of them are being sent to the consortium's central library in Scotland

© EMD

Searching for substances

Joining forces to find new active ingredients

2013/6/18

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To date, pharmaceutical companies have searched in their own inventories for new active ingredients for medicines. Now, however, they are pooling their compound libraries in the European Lead Factory, a development platform established by the EU's Innovative Medicines Initiative.

The search for new efficacious medicines has become even more efficient. The European Lead Factory is a consortium of seven of Europe's major pharmaceutical companies together with 23 biotech firms and a range of academic institutions. Its purpose is to compile a consortium library of the hundreds of thousands of chemical compounds in the inventories of these organizations. Subjecting these compounds to a procedure known as high-throughput screening will boost the chances of discovering new active ingredients.

  • Mirek Jurzak coordinates EMD's participation in the European Lead Factory
  • Mirek Jurzak coordinates EMD's participation in the European Lead Factory
    © EMD

    A major effort for tiny amounts of compounds


    Mirek Jurzak is coordinating EMD's involvement in the platform, which also includes the participation of Bayer, AstraZeneca, Sanofi, UCB Pharma, H. Lundbeck, and Janssen Pharmaceuticals. These seven major pharmaceutical companies are being joined by various biotech firms and academic institutions, including the Scottish bioscience incubator BioCity, where the consortium library will be compiled, and the nonprofit organization TI Pharma, based in the Netherlands, where a total of 48 high-throughput screenings are to be conducted each year.

    The project, which is called the European Lead Factory, will be funded with a total of EUR 196 million over a period of five years. "It was the European Union's Innovative Medicines Initiative that finally gave us the opportunity to implement this long-cherished idea," says Jurzak. The technical challenges facing the project are substantial. Each company has its own procedures for handling compounds, with different types of containers to store dissolved substances, and different kinds of screening methods.

    The project therefore requires a uniform system that is also flexible enough to accommodate the different screening robots of each consortium partner. The seven pharmaceutical companies are sending a total of 300,000 compounds to the central library in Scotland. "We have around 20 copies of every compound in our own library, and we are committed to providing the consortium with seven copies of each one," Jurzak explains.

    The consortium library in Scotland archives these and also produces further copies, so that the screening center in the Netherlands and each consortium partner can receive samples for testing purposes. Microliter-sized samples of the solutions are transported in standard microtiter plates containing up to 1,536 wells — like the baking trays for muffins, but smaller.

    This process will ultimately result in the Joint European Compound Collection. Each of these compounds will then undergo a variety of test procedures, known as assays, in order to investigate their effect on human cells, for example. If a compound is able to attach itself to a specific pathogenic target molecule, it thereby demonstrates its potential as a "lead" for drug development. The purpose of the European Lead Factory is to identify as many leads as possible.
    During high-throughput screening, tens of thousands of compounds are examined in the search for new active ingredients

    During high-throughput screening, tens of thousands of compounds are examined in the search for new active ingredients

    © EMD

    Expanding the chemical space

    2013/6/18

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    Throughout 2013, EMD will be integrating these compounds into ongoing tests whose aim is to find effective compounds for treating diseases such as cancer, immune system disorders, and multiple sclerosis. EMD will also be using compounds from other consortium partners in screenings that have so far failed to identify a suitable active ingredient from within its own compound library.

    According to Jurzak, one of the reasons for this is that "chemical space" covered so far by the pharmaceutical companies’ individual compound libraries is minuscule in comparison to the theoretically possible number of compounds that are medically relevant. "It is estimated that these compounds can be combined to form between 1040 and 1060 new drugs — more than the number of atoms in the universe," he says.

    The consortium's first objective is therefore to expand the chemical space in which the search for potential active ingredients for medicines is pursued. Because this requires more than merely amalgamating existing compound libraries, the European Lead Factory has also invited academic institutions to submit proposals for novel chemical compounds.

    The aim is to compile chemical libraries on a completely new scale. As Jurzak explains, these might then contain more three-dimensional molecular structures, as is the case in nature, since to date the chemical processes used by the pharmaceutical industry have tended to yield planar structures. The consortium is hoping to develop some 200,000 new compounds, with the result that the Joint European Compound Collection will ultimately comprise around half a million compounds.

    Jurzak is passionate about the project. "There has never before been a public-private partnership on this scale in the pharmaceutical industry!" he says. "This is virgin territory for everyone concerned and an exciting experiment. One major challenge is to ensure that any patent claims on compounds held by individual companies are settled in the interest of the consortium. So far we have always been able to reach a compromise."

    Jurzak's hope is that an early and open exchange of knowledge among the consortium partners will produce results that benefit everyone, especially patients. "We will be truly delighted if marketable new medicines resulted thanks to this consortium, even if initially it were just only a single one," he says.

     
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