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| About Stephen Burley (SGX Pharmaceuticals) |
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Stephen Burley M.D., D.Phil., F.R.S.C. is the chief scientific officer of SGX Pharmaceuticals, Inc. (SGX; http://www.sgxpharma.com/), located in San Diego, California. SGX is an oncology focused drug discovery and development company, with multiple protein kinase inhibitors in preclinical development, including compounds targeting imatinib resistant BCR-ABL, c-MET, and JAK2. Prior to joining SGX, Burley was the Richard M. and Isabel P. Furlaud professor and chief academic officer at The Rockefeller University, and a full investigator in the Howard Hughes Medical Institute. He has authored or coauthored more than 175 scholarly scientific articles. He is a fellow of the Royal Society of Canada and of the New York Academy of Sciences. Burley received an M.D. degree from Harvard Medical School in the joint Harvard-MIT Health Sciences and Technology program and, as a Rhodes Scholar, received a D.Phil. in Molecular Biophysics from Oxford University. He trained in internal medicine at the Brigham and Women's Hospital, and did post-doctoral work with William N. Lipscomb at Harvard University and Gregory A. Petsko at the Massachusetts Institute of Technology. With William J. Rutter and others at the University of California, San Francisco and The Rockefeller University, Burley co-founded Prospect Genomics, Inc., which was subsequently acquired by SGX
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Fragment-based discovery of selective, orally bioavailable tyrosine kinase inhibitors for targeted treatment of human cancers
Stephen K. Burley, Chief Scientific Officer and Senior Vice-President Research, SGX Pharmaceuticals, Inc., 10505 Roselle Street, San Diego, CA 92121
SGX Pharmaceuticals, Inc. (SGX) has developed a fragment based drug discovery platform that utilizes high-throughput X-ray crystallography for lead identification/optimization. The proprietary FAST™ (Fragments of Active Structures) 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 our 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.
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