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BioFocus DPI e-update summer 09
It is my great pleasure to share with you the first BioFocus DPI e-update for clients and the wider drug discovery community.
We are living through a time of unprecedented change in how and where we do the discovery that will generate tomorrow’s medicines. With only about 15 major pharma companies remaining, there have arisen three new places where research is performed with vigour - biotech, charities and contract research houses.
When I began in the industry 30 years ago, drug discovery was performed almost exclusively in the research laboratories of what would today be called small- to middle-sized pharmaceutical enterprises. Nearly all of these are long vanished as independent corporations (May and Baker, Burroughs Wellcome, Rorer, Marion Merrill Dow, Laboratoires Fournier, Boehringer Mannheim, to name but a few) subsumed into gigantic enterprises like Pfizer, Merck, GSK and Takeda, which still retain a voracious appetite for further consolidation.
With about 15 such gigantic pharmaceutical businesses remaining, there have arisen three other types of places where research is now performed with vigour: i) biotech – companies ranging in size from a few to many hundreds of research scientists (e.g. Galapagos, Prolysis, FoldRx, Metabolex), ii) charities which may be virtual or have their own bricks and mortar (e.g. CHDI, CF Foundation, CR UK) and iii) contract research houses (e.g. BioFocus DPI, AMRI, Wuxi, GVK Bio, Argenta, Cerep). To my mind, pharmaceutical research is more powerful as a consequence, all enterprises depend on each other, and the vibrant commercialization of research has stimulated a more pressured environment where the choice of project from the vast plethora of possibilities, is critical to the success of the enterprise.
BioFocus DPI is staffed by people with diverse backgrounds – this intermixing of skills is required to recommend and choose the best projects and strategies for execution. This opening of minds remains critical in drug research. In this, the fastest evolving of scientific disciplines, never was the adage that “no man is an island” more true. We remain committed to the latest technologies, and if we do not have them in house, we have a network of alliances to bring in that capability to our clients’ programs. By example, through our Dutch partner ZoBio we offer a NMR screening platform and TINS technology, which is coupled with BioFocus DPI’s structural biology. This gives an unprecedented new capability in fragment based drug discovery. Further details of our network of alliances with companies like Cresset Biomolecular, California Stem Cells, and Oncodesign can be found on this website.
Chris Newton
Senior VP BioFocus DPI
Free: Novel Alzheimer's target discovered
Get a free copy of the original paper
A recent paper in the journal Science describes the identification of a new drug target that affects the production of beta-amyloid, a protein that is believed to cause Alzheimer’s disease. This significant discovery came from a high-throughput screen of over 1,900 unique genes encoding potential drug targets from BioFocus’s FLeXSelect collection.
To find out more about this research, request your free reprint of this Science paper. Find out more about FLeXSelect and our target discovery capabilities.
BioFocus® and FLeXSelectTM are trademarks of Galapagos NV and/or its affiliates.
GPCR conference
22-23 September 2009, Chesterford Park, Saffron Walden, near Cambridge, UK
This conference will highlight the latest technological developments and tools available for drug discovery on GPCR receptors, with key opinion leaders presenting their experience of generating high-quality screening data. Case studies will describe how flexible assay formats and newly available tools have enhanced throughput for successful compound screening. Poster submissions are encouraged.
Attendance is free but is limited to 150 delegates, so book early to avoid disappointment.
Enhanced: ADME/PK analysis times down; throughput up
Since the start of the year we have significantly strengthened our ADME/PK Laboratory bioanalytical capabilities.
Our new Waters® Xevo™ TQ Mass Spectrometer and UltraPerformance LC system has reduced analysis times and increased sample throughput, in a wide range of biological matrices. Enhanced sensitivity also helps identify metabolites present at low levels. Clients have already benefitted, with one client in particular experiencing a significantly reduced time to develop the analytical methods for a bespoke assay.
Earlier this year we broadened our range of “off the shelf” ADME/PK assays with the addition of CYP2C8 to our list of Cytochrome P450 isoforms available for inhibition studies. We also offer induction assays for Cytochrome P450 isoforms CYP1A2, CYP3A4 and CYP2B6.
New assay development continues: an assay is now available to study the percentage compound bound to brain homogenate and additional endpoints of cytoxicity (LDH and caspase 3/7) have been developed to complement the existing ATP measurement. And, in the autumn, we will launch an additional in vitro assay that mimics some aspects of blood-brain barrier penetration - adding to the essential information we can provide to CNS projects.
For more information on our ADME/PK capabilities please contact us.
New: Major developments in our compound libraries
We have recently launched six new, carefully-engineered SoftFocus libraries that specifically target ion channels, kinases and proteases. In addition, we have just added 350,000 new compounds to complement our existing diverse screening library, so our high-throughput screening platform now includes over 900,000 unique compounds.
The new SoftFocus SFI13 ion channel library has been designed using our Helical Domain Recognition Analysis (HDRA) approach, which links X-ray, sequence alignment and SAR data. HDRA is used to rationalize scaffold binding in the pore regions of ion channels and to guide monomer selection. The four new kinase libraries (SFK54, SFK55, SFK56 and SFK57) have been developed to target hinge, DFG-out and novel binding modes. Finally the new SFP03 protease library targets cysteine and serine proteases, and is designed using a new technique based upon structures of more than 50 protease-ligand complexes available from the Protein Data Bank.
For more information on our compound libraries please contact us.
Update: Successful structural biology service continues to evolve and provide ever-greater capabilities
Kate Hilyard VP Biological Sciences
The BioFocus DPI structural biology platform was already established when we acquired it from Sareum in August last year. The platform supports structure-based drug discovery from the protein expression of targets of interest through to final structure determination – including incorporation of client-selected ligands.
Our team of experienced scientists employs the latest techniques, backed up by the best equipment. Our expertise covers high-throughput protein expression using insect and bacterial systems, automated protein purification and crystallization, and X-ray crystallography and structure determination. We work with novel targets, or with examples from the Protein Database (PDB), as well as our in-house structure library, Crystal Bank, for which we can generate target/ligand complex structures within 2 to 3 weeks.
To complement our X-ray platform we now also offer fragment screening. We have built a fragment library for which the experimental aqueous solubility of 1,000 fragments has been determined. This library is available for high concentration biochemical screening and for direct binding assays on our Biacore T100 instrument. In addition, we are now also able to provide fragment-based NMR screening through an agreement with ZoBio, a company with extensive experience in fragment-based screening using its patented Target Immobilized NMR Screening (TINS) technology.
All these approaches allow our team to rapidly screen drug fragment libraries with high sensitivity using only a few mg of target protein. Our X-ray platform is then used to determine the target/fragment structures that can then be taken forward into a fragment-to-lead optimization programme.
For more information on our structural biology capabilies please contact us.
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