Coordinated TAKTIC

Six-way partnership attempts synergy in inhibiting protein kinases to develop novel drugs

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LUND, Sweden—It began with a 2010 conversation about apotential biotechnology industry-academia collaboration to enhance proteinproduction capabilities. Now a six-member drug discovery partnership fundedwith $1.5 million from the European Union (EU) will target protein kinases totreat cancer, diabetes and inflammatory diseases. 
The Translational Kinase Tumor Inhibitor DiscoveryConsortium (TAKTIC) brings together the proprietary technologies of threeexpert organizations in the field of drug discovery with extensive expertise inmedicinal chemistry, kinase biochemistry and biology and a state-of-the-art high-throughputplatform for protein expression and crystallization. The consortium includesSweden's SARomics Biostructures, France's Prestwick Chemical and Germany'sProQinase GmbH, along with the University of Turin, Italy, the IsraelStructural Proteomics Center at the Weizmann Institute and the TechMedIllplatform of the University of Strasbourg, France.
The merging of the highly complementary capabilities of thepartners enables an efficient and versatile kinase drug discovery platform thatwill target some challenging and medically important kinases, according toProf. Salam Al-Karadaghi, project coordinator and director of businessdevelopment at SARomics Biostructures. 
"We are excited to coordinate a frontline project of thesedimensions, which brings together companies and academic researchers withimpressive track records within their respective fields," he says.
Protein kinases make up 1.7 percent of all human genes andinclude more than 500 family members. They play a key role in regulating cellularprocesses. When unregulated, they can cause several disease states. While bothmutated and activated protein kinases have proven to be useful targets for thedevelopment of new anticancer therapies, achieving selective inhibition ofspecific protein kinases can be challenging.
As Dr. Michael Kubbutat, head of biochemical drug discoveryand head of drug development at ProQinase, explains, "the consortium iscoordinated by SARomics Biostructures. Whereas the main body of work will beperformed by the academic partners, the companies will manage the project andwill contribute some key technologies to the project."
Kubbutat says SARomics, of Lund, Sweden, a leadingScandinavian provider of structural biology and in-silico drug discovery services, will contribute itscomprehensive expertise in structural biology and will closely interact withthe Israel Structural Proteomics Center at the Weizmann Institute of Science,in Rehovot, Israel, which serves as an Israeli National Center for proteinproduction, biochemical/biophysical studies and structure determination, andwill produce highly purified proteins suitable for crystal structure analysis.
Kubbutat adds that Prestwick Chemicals, a France-basedmedicinal chemistry company that successfully identifies hits and optimizesthese into clinical candidates, will contribute its know-how in the field ofmedicinal chemistry, as well as compound libraries that will serve as astarting point for the discovery of new drugs. Prestwick will closely interactwith the Medicinal Chemistry unit of the University of Torino, which hasextensive expertise in the chemical optimization of kinase inhibitors, and willperform the medicinal chemistry optimization. 
ProQinase, a contract service provider dedicated tosupporting pharmaceutical and biotech companies in the development of noveltherapies for cancer treatment, will closely interact with the BiochemistryUnit of the University of Torino, which will perform biochemical and cellulartesting of compounds. ProQinase has an established high-throughput screeningfacility and will perform high-throughput primary screening and contribute itsbiological know-how in the development of protein kinases inhibitors. TheTechMed unit of the University of Strasbourg, France, will perform preclinicalADME-toxicity testing of the optimized compounds.
The project has a timeframe of two years, according toKubbutat. The aim of the collaboration, he says, is the discovery andoptimization of novel compounds inhibiting three protein kinases that areinvolved in the regulation of the transcription factor NF-kB, a key regulatorof tumor cell growth. The expected results comprise different novel chemicalclasses of protein kinase inhibitors that can serve as starting points for thedevelopment of novel anticancer drugs.
As to the commercial potential, Kubbutat says, "the newlyidentified protein kinase inhibitors will represent valuable starting pointsfor the development of novel anticancer drugs, and by this represent asignificant value for pharmaceutical companies.  Furthermore, novel technologies in protein structureanalysis and biochemical and cellular assays will be developed and will becommercialized by the involved biotech companies."

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