PRLog (Press Release) –
Oct 17, 2007 – MONROVIA, CA – Dr. Stephen K. Burley, Chief Scientific Officer and Senior Vice-President Research at SGX Pharmaceuticals, Inc. located in San Diego, CA will give the Keynote presentation at GTCbio’s Drug Design & Lead Discovery conference – one of six tracks at the 3rd Modern Drug Discovery & Development Summit on November 28-30, 2007 at the Hyatt Regency San Francisco Airport.
Dr. Burley’s presentation will cover fragment-based discovery of selective, orally bioavailable tyrosine kinase inhibitors for targeted treatment of human cancers with examples from SGX’s FAST™ (Fragments of Active Structures) platform.
The fragment-based drug discovery platform utilizes high-throughput X-ray crystallography for lead identification/
optimization. The process exploits crystallographic screening to detect, visualize and identify small ligands (MW 150-200) that are bound to the target protein. Each member of the FAST™ fragment/scaffold library was selected to be amenable to rapid chemical elaboration at two or three points of chemical diversity using parallel organic synthesis. Initial lead optimization involves using SGX’s knowledge of the co-crystal structure of the target-fragment complex and advanced computational chemistry tools to guide synthesis of small focused linear (one-dimensional) libraries. These linearly elaborated fragments/scaffolds are then evaluated with in vitro biochemical and cellular assays and co-crystal structure determinations. Thereafter, optimal variations at each point of chemical diversity are combined to synthesize focused combinatorial (two- or three-dimensional) libraries that are again examined with assays and crystallography. (The potential chemical diversity of the fully elaborated FAST™ fragment/scaffold library far exceeds 160 million compounds.) Active compound series are prioritized for further medicinal chemistry and compound development efforts using the results of in vitro and in vivo ADME and in vitro toxicology studies. Successful applications of the FAST™ fragment-based lead discovery/optimization process will be presented for a portfolio of well validated oncology targets.
The 3rd Modern Drug Discovery & Development Summit features over 150 speakers participating in 6 concurrent conferences, 6 study sessions and 3 pre-conference workshops. Tracks include Biological Therapeutics, Drug Delivery Technology, Translational Medicine, Drug Design and Lead Optimization, Emerging Targets, and Pharmaco – Kinetics, Dynamics, Genomics and Genetics. For more information, visit www.gtcbio.com.
