A long awaited facility

The Lyon Cancer Research Center (CRCL) and the Léon Bérard Center (CLB) joined together with the Synergie Lyon Cancer Foundation to set up the Drug Discovery and Development Center (C3D), to satisfy the long long-expressed needs of the network of 150 internationally acknowledged researchers in Lyon.

This pharmaceutical research center dedicated to cancerology is located on the CLB site and completes the technological facilities at the interface between fundamental and clinical research already funded and set up by the Synergie Lyon Cancer Foundation, such as the bioinformatics center and the tumour model laboratory (LMT). 

Pooling resources at the service of innovation

The goal of the Drug Discovery and Development Center is to give fundamental research teams that have discovered a gene, protein or a signaling pathway involved in the development of cancer, tools for defining molecules of interest known as “candidate drugs” acting against this target. The availability of this center at the core of research and care in Lyon allows scientists to: 

• accelerate the transfer of the results obtained by fundamental research to applied research,
• facilitate the implementation of clinical studies and performing further studies of drugs liable to cover as yet unsatisfied medical needs. 

The Drug Discovery and Development Center has been designed to better satisfy the expectations of industrial companies regarding academic research in the commercial development of molecules: provide validated data and proof of concepts in a state as finalized as possible for a potential drug,

Sylvie Négrier, General Manager of the CLB and instigator of the Drug Discovery and Development Center.

An environment of expertise in cancerology

Under the management of Stéphane Giraud, the Drug Discovery and Development Center offers researchers a high level scientific and medical environment as well as innovative infrastructures. It has its own technological installations and the multidisciplinary competences (biology, medicinal chemistry, non-clinical development) needed to drive a pharmaceutical research project.

Endowed with all the equipment indispensable for biochemistry, molecular biology, the manipulation of all types of cell and a collection of tens of thousands of molecules, the center has recently acquired a robot that is used to test the effect of hundreds and even thousands of compounds in a single day. The center’s equipment is completed by two mass spectrometers dedicated to the detection and analysis of molecules in complex media such as blood plasma.

Initiated in 2010 by Sylvie Négrier to promote clinical applications based on the results of Lyonnais cancer researchers, the drug discovery and development center was built by a group of researchers from the Léon Bérard Center and the Lyon Cancer Research Center.

A need long identified by the Lyonnais medical-scientific network

The need for a Drug Discovery center in Lyon was transformed in 2010 into a project instigated by Sylvie Négrier, the General Manager of the Léon Bérard Center (CLB). Aware of the dual competences in science and industrial applications of Alain Puisieux, Patrick Mehlen, Christophe Caux, Jean-Guy Delcros and Jean-Jacques Diaz, Sylvie Négrier called on them to set up the project and form the interface between the researchers of the CLB, the Lyon Cancer Research Center (CRCL) and potential industrial partners. Finally, the Drug Discovery center obtained funding in 2012 due to the flexibility and the capacity for rapid decision-making of the Synergie Lyon Cancer Foundation and to the solid financial and scientific support of the CLB and the CRCL.

Design by researchers with acknowledged expertise in the problem

 Jean-Jacques Diaz and Jean-Guy Delcros worked to speed up the scientific and technical construction of the Drug Discovery and Development Center under the supervision of Marina Rousseau-Tsangaris:

Jean-Jacques Diaz, Director of Research at the Inserm and responsible for the “Nuclear Medicine and Diseases” department at the CRCL, has collaborated since his doctoral thesis in 1988 with private R&D departments in view to transferring knowhow. “I wanted to find a concrete outlet for my discoveries as quickly as possible”, he recalls.

Only a small number of the results obtained by the academic research team can be used for applied research. With the Drug Discovery Center, the resources we need are now available at the core of fundamental research in Lyon, to identify candidate drugs in close collaboration between researchers.

Jean-Jacques Diaz

Jean-Guy Delcros is a researcher in the Apoptosis, Cancer and Development team of the CRCL managed by Patrick Mehlen. Since he started his work, he has been frequently confronted with the problem of finding competences and tools quickly to develop potential drugs for the targets he finds. “The project of the Drug Discovery Center satisfies a personal objective”, he says. “It allows me to avoid going to industrial companies with the likelihood that my results are too far upstream for them”. He is now providing advice to the center’s operational manager to evaluate the best experimental approach to adopt as a function of each project and its objectives.

Production, starting up and selecting the first projects of the Drug Discovery Center

After their contribution to writing the file and designing the project, the group of researchers responsible for building the Drug Discovery and Development Center started setting up the center by purchasing equipment, and recruiting Stéphane Giraud, the operational manager, and Laetitia Martin, a laboratory technician.

Using a target identified by fundamental research, developing a drug starts by auditioning thousands of molecules in order to cast the right one.

Between scientific research and initial experiments

As part of the drug development process, the Drug Discovery and Development Center intervenes in every step between fundamental research and clinical research. The role of a drug discovery center is to seek promising molecules for developing drugs.

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The details of the process and an example for better understanding

A university (or fundamental) research team discovers and validates a “target” (gene, protein, enzyme, etc.) of an organism involved in a specific cancer. Using different models, it has shown that a beneficial effect can be envisaged by acting on this target, for example, by inhibiting its expression. The first aim is therefore to find a molecule that presents this inhibiting effect in order to test the therapeutic project on a living organism.

Thus the step involving the identification of such a molecule starts. This step is itself broken down into successive phases that conform to defined protocols:

1. The choice and development of an in vitro test performed to visualize (by fluorescence, luminescence, etc.) and measure the activity of the target in a microplate well: for example, the production of an enzyme from its substrate.
2. Bringing the product into contact with the molecules:
   • Today, most drugs are still identified by screening molecular banks. The drug discovery center has several tens of thousands of compounds that are used to “screen” the test product and a robot that analyses thousands of these compounds per day.
   • A rational method based on the known scientific data of the target is used. By employing in silico modeling tools (on computer models), a virtual molecule is drawn in order to design pertinent atomic bonds.
3. After isolating (or identifying) the “hit” compounds showing interesting effects, new tests are performed to measure the effect-dose and verify the physicochemical properties of the molecules.
4. Optimization by medicinal chemistry of the molecular structure of the hits to improve their activity on the target and their behavior in vivo (toxicity, bioavailability, etc.).

Thus we obtain lead compounds (starting points) that will be tested on experimental cancer models.If good preliminary results are obtained, the program to develop the drug can begin.

The Drug Discovery and Development Center makes available tools that are immediately operational for researchers and manages the subcontracting required to accelerate the transformation of the targets identified into candidate drugs. We have the expertise to treat each file entrusted to us up to the clinical phase.

Stéphane Giraud, operational manager of the Drug Discovery Center.