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LUND, Sweden—It began with a 2010 conversation about a potential biotechnology industry-academia collaboration to enhance protein production capabilities. Now a six-member drug discovery partnership funded with $1.5 million from the European Union (EU) will target protein kinases to treat cancer, diabetes and inflammatory diseases.
The Translational Kinase Tumor Inhibitor Discovery Consortium (TAKTIC) brings together the proprietary technologies of three expert organizations in the field of drug discovery with extensive expertise in medicinal chemistry, kinase biochemistry and biology and a state-of-the-art high-throughput platform for protein expression and crystallization. The consortium includes Sweden's SARomics Biostructures, France's Prestwick Chemical and Germany's ProQinase GmbH, along with the University of Turin, Italy, the Israel Structural Proteomics Center at the Weizmann Institute and the TechMedIll platform of the University of Strasbourg, France.
The merging of the highly complementary capabilities of the partners enables an efficient and versatile kinase drug discovery platform that will target some challenging and medically important kinases, according to Prof. Salam Al-Karadaghi, project coordinator and director of business development at SARomics Biostructures.
"We are excited to coordinate a frontline project of these dimensions, which brings together companies and academic researchers with impressive track records within their respective fields," he says.
Protein kinases make up 1.7 percent of all human genes and include more than 500 family members. They play a key role in regulating cellular processes. When unregulated, they can cause several disease states. While both mutated and activated protein kinases have proven to be useful targets for the development of new anticancer therapies, achieving selective inhibition of specific protein kinases can be challenging.
As Dr. Michael Kubbutat, head of biochemical drug discovery and head of drug development at ProQinase, explains, "the consortium is coordinated by SARomics Biostructures. Whereas the main body of work will be performed by the academic partners, the companies will manage the project and will contribute some key technologies to the project."
Kubbutat says SARomics, of Lund, Sweden, a leading Scandinavian provider of structural biology and in-silico drug discovery services, will contribute its comprehensive expertise in structural biology and will closely interact with the Israel Structural Proteomics Center at the Weizmann Institute of Science, in Rehovot, Israel, which serves as an Israeli National Center for protein production, biochemical/biophysical studies and structure determination, and will produce highly purified proteins suitable for crystal structure analysis.
Kubbutat adds that Prestwick Chemicals, a France-based medicinal chemistry company that successfully identifies hits and optimizes these into clinical candidates, will contribute its know-how in the field of medicinal chemistry, as well as compound libraries that will serve as a starting point for the discovery of new drugs. Prestwick will closely interact with the Medicinal Chemistry unit of the University of Torino, which has extensive expertise in the chemical optimization of kinase inhibitors, and will perform the medicinal chemistry optimization.
ProQinase, a contract service provider dedicated to supporting pharmaceutical and biotech companies in the development of novel therapies for cancer treatment, will closely interact with the Biochemistry Unit of the University of Torino, which will perform biochemical and cellular testing of compounds. ProQinase has an established high-throughput screening facility and will perform high-throughput primary screening and contribute its biological know-how in the development of protein kinases inhibitors. The TechMed unit of the University of Strasbourg, France, will perform preclinical ADME-toxicity testing of the optimized compounds.
The project has a timeframe of two years, according to Kubbutat. The aim of the collaboration, he says, is the discovery and optimization of novel compounds inhibiting three protein kinases that are involved in the regulation of the transcription factor NF-kB, a key regulator of tumor cell growth. The expected results comprise different novel chemical classes of protein kinase inhibitors that can serve as starting points for the development of novel anticancer drugs.
As to the commercial potential, Kubbutat says, "the newly identified protein kinase inhibitors will represent valuable starting points for the development of novel anticancer drugs, and by this represent a significant value for pharmaceutical companies. Furthermore, novel technologies in protein structure analysis and biochemical and cellular assays will be developed and will be commercialized by the involved biotech companies."