SAN DIEGO--(BUSINESS WIRE)--Nov. 18, 2002--Syrrx Inc., a next generation rational drug discovery company, has determined the detailed atomic structures of three cancer-associated proteins: Aurora-A kinase, focal adhesion kinase (FAK) and ephrin receptor A2 (EphA2). Syrrx is using atomic resolution data from these structures to aid in the design of potential drugs to treat breast cancer, prostate cancer, colon cancer, melanoma, and thyroid carcinoma. Information regarding these discoveries is being published in the November, 2002 issue of the journal Structure (http://www.structure.org/).
The structures were determined using Syrrx's high-throughput structural biology (HTSB) platform, which uses state-of-the-art automation and Syrrx's Nanovolume Crystallization(TM) technology to crystallize disease-causing proteins. The use of Syrrx's proprietary submicroliter crystallization technology was central to the company's successful protein structure determination efforts. Some advantages of submicroliter crystallography include the use of less protein for crystallographic experiments, accelerated crystal growth, and the formation of more ordered crystals to enhance the ultimate quality of the structures determined. "We determined the structures of these proteins to decrease the time required to design potent inhibitors of these drug targets," explained Duncan McRee, Director of Crystallography at Syrrx. "And our submicroliter crystallography approach enabled the rapid generation of structural data, which is a key tool in modern drug discovery."
EphA2, FAK, and Aurora-A are human proteins centrally involved in tumor growth and metastasis (the ability of a tumor to spread throughout the body). Each of these proteins are potential drug targets because their activity is thought to cause (or exacerbate) multiple types of cancer. "These proteins represent attractive targets for the design of new cancer therapies," said Jacek Nowakowski, Ph.D., a senior scientist at Syrrx and first author on the paper. "In addition," added Devon Thomson, Ph.D., senior scientist and co-author, "we can now scrutinize these three-dimensional structures to understand their differences, which will help us design exquisitely potent and selective kinase inhibitors to treat cancer."
The Syrrx HTSB technology platform uses novel, proprietary tools that bypass historical bottlenecks in the classical protein structure determination process. Deployed in a streamlined, automated environment, Syrrx technology enables the determination of protein structures more reliably and quickly than ever before possible. For the past year, Syrrx has been determining the 'shape' of one unique cancer-related kinase every three weeks and has used these 'shapes' to design proprietary drugs of such potency that they are active even at nanomolar concentrations.
The authors of the Structure paper are Jacek Nowakowski, Ciaran N. Cronin, Duncan E. McRee, Mark W. Knuth, Christian Nelson, Nikola P. Pavletich, Joe Rogers, Bi-Ching Sang, Daniel N. Scheibe, Ronald V. Swanson, and Devon A. Thompson.
About the Syrrx Drug Discovery Portfolio
Syrrx focuses on drug targets that have been validated in human clinical trials. Many of these so-called 'high validation state' drug targets, despite their demonstrated utility as points of disease intervention, have resisted industry-wide efforts to determine their 3D 'shapes.' Syrrx exploits its competitive advantage in high-throughput structural biology to be the first organization to determine these 'shapes' and then uses them as starting points for iterative, structure-based drug design to produce "best-in-class" drug candidates.
About Syrrx Inc.
Syrrx, Inc. is a drug discovery company redefining the way medicines are discovered. Based in San Diego, CA, the company is at the forefront of rational drug discovery and is currently directing its efforts toward developing therapeutics to treat cancer, inflammation, and metabolic diseases. Syrrx leverages high-throughput structure determination, screening, combinatorial and medicinal chemistry together with computational methods to discover novel small molecule drug leads. In combination, these proprietary technologies form a unique "gene to drug" platform that enables parallel rational drug discovery programs. Syrrx has structural proteomic and drug discovery collaborations with industry leaders, including Sankyo Co. Ltd., Hoffman-La Roche Ltd., Pharmacia Corporation, Celera Genomics Group, and Cubist Pharmaceuticals. The company has also acquired small molecule assets from Onyx Pharmaceuticals for use in internal discovery programs at Syrrx. For more information, please visit the Syrrx website at syrrx.com. |
