The consortium aims to identify and develop new drugs for the inhibition of tumour angiogenesis using the aptamer-based approach, which will integrate the technology platforms of the three companies. In using these techniques in structural target validation and lead optimisation, the time to market is substantially reduced saving costs per drug and rate of failure.
Aptamers are synthetic nucleic acid ligands that fold into defined 3-D shapes and bind target proteins with nanomolar affinities and high specificities. Inhibitory aptamers have been used for target validation in cell culture and animal models with excellent results. Furthermore, they can be easily integrated into rational drug design approaches or HTS to identify small molecule inhibitors.
The collaboration will combine Xantos' target discovery and small molecule screening technology, PSF biotech's protein production and crystallisation capabilities and NascaCell's aptamer technology for target validation and drug discovery.
"This project will enable us to apply our efficient high-throughput technologies to find new targets and therapies against cancer," Dr Ulrich Brinkmann, CSO of Xantos, commented.
"Having provided potential protein targets to our partners for their added value, our XantoScreen platform is the ideal tool to identify promising small molecules derived from interacting aptamers, with the goal to find new therapeutic approaches," he added.
The development of new drugs for the inhibition of tumour angiogenesis is an area that is gaining momentum within the industry. Avastin (Bevacizumab) is the product of a joint development programme between Genentech and Roche, Avastin (bevacizumab) is a humanised monoclonal antibody (MAb) directed against vascular endothelial growth factor (VEGF), a pro-angiogenesis factor.
Avastin broke new ground in becoming the first angiogenesis inhibitor to market when it secured US FDA approval at the end of February 2004 for use as a first-line treatment with 5-FU for patients with metastatic colorectal cancer.
In January 2005, Avastin received European approval for first-line use in patients with metastatic colorectal cancer, with patients in Germany, Switzerland and the UK among the first to receive this new cancer treatment.
The three technologies that will play a central role in this consortium include Xantos has established the cellular gene-transfection and assay system XantoScreen that is used for several functional applications including molecular drug profiling, target / pathway profiling, target and protein identification as well as lead identification.
NascaCell's automated in vitro selection platform, SELEX allows the rapid generation of aptamers for almost any target of choice (e.g. kinases, proteases, growth factors, and protein-protein interactions). To meet the requirements of different applications NascaCell offers characterised and bio-stable aptamers with different kinds of site-specific labels (e.g. fluorescent dyes, affinity tags).
PSF's technology platform consists of bioinformatics modules, protein production units with various host systems, biophysical characterization units, NMR spectroscopy and synchrotron-based protein crystallography to provide structural insight with high quality and high throughput.
Based on the 3D-structure of a protein target, the mechanism of agonism and antagonism can be understood; specific binders can be identified and subsequently modified to yield high quality lead candidates for new drugs.