High Throughput Kinase Screening Expedites Drug Discovery and Development

Innovation Perspective Paper Published in Nature Reviews Drug Discovery

San Diego – April 23, 2008 - Traditional approaches to developing drugs that target kinases rely on selecting a single kinase of interest and finding a compound that inhibits it, a time consuming and resource-intensive process. The new approach of high throughput kinase profiling gives drug developers a tool to make kinase-focused drug discovery more efficient and cost effective.

Kinases are among the most important drug targets. They are essential for the normal regulation of cellular function, and abnormal kinase activity is implicated in cancer, inflammation, metabolic disorders and other diseases. There are eight small molecule kinase inhibitors on the market today generating over $5 billion in annual sales.

In an Innovation Perspective article published in the journal Nature Reviews Drug Discovery, scientists now describe how high throughput kinase profiling guides and accelerates the identification of high-quality lead compounds against kinase drug targets. The article, entitled "High-throughput kinase profiling as a platform for drug discovery," is featured in the May issue and is available online now.

In the traditional approach to drug discovery, companies select a target kinase of interest and then screen libraries of thousands of compounds against that target. Using this approach, it remains unknown whether compounds in the library may be more effective inhibitors of another, potentially equally therapeutically relevant kinase, and the best starting points for drug development may be overlooked. The application of high throughput kinase profiling, in contrast, incorporates screening of compound libraries against all potential kinase drug targets at once, providing a complete view of all opportunities afforded by compounds in the library. This allows:

• Comprehensive functional annotation of entire kinase-focused compound libraries
• Recognition of the highest quality leads in a compound library
• Identification of new chemical structures that inhibit kinases
• Focus of discovery resources on projects most likely to succeed

"High throughput kinase profiling technology has provided Cephalon, in its collaboration with Ambit Biosciences, with an extremely cost-effective and rapid means by which to generate the activity ‘fingerprint’ for novel compounds as kinase inhibitors," stated Mike Williams, Ph.D., D.Sc., vice president of worldwide discovery research of Cephalon, Inc. "The flexible nature of Ambit’s KINOMEscan™ approach, in particular, helps guide our medicinal chemistry efforts by optimizing compounds for activity and selectivity, matching targets of therapeutic interest with high quality hits, and facilitating and expediting project prioritization. Ambit’s compound-centric approach also provides a means to actively exploit Cephalon’s kinase-optimized compound libraries and identify tool compounds with which to validate kinase targets."

About KINOMEscan™

KINOMEscan™ is the industry's most comprehensive high-throughput system for screening compound libraries against large numbers of human kinases. KINOMEscan™ employs proprietary active-site dependent competition binding assays to determine how compounds bind to both intended and unintended kinases targets. In addition to helping keep discovery programs on target, KINOMEscan™ screens can opportunistically identify unanticipated interactions that can expand the therapeutic utility of compounds or serve as advanced starting points for new programs. Ambit's largest panel, scanMAX™, with more than 400 assays, is the world's largest kinase profiling panel.

Ambit's KINOMEscan™ Division provides custom kinase profiling services to drug companies in addition to supporting the company's separate, internal drug development programs. KINOMEscan™ is a key component of Ambit's partnerships with Roche, Bristol-Myers Squibb, Cephalon, and others. The technology has been featured in papers published in Nature Biotechnology and The Proceedings of the National Academy of Sciences of the United States of America. For more information, please visit www.kinomescan.com.

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company engaged in the discovery and development of small molecule kinase inhibitors for the treatment of cancer. The company also markets the industry's most comprehensive kinase profiling service through its KINOMEscan™ Division. KINOMEscan is a proprietary technology designed to screen small molecule libraries against large numbers of human kinases. Ambit has multiple drug candidates in pre-clinical and clinical development, including AC220, a selective class III receptor tyrosine kinase inhibitor currently in Phase I for treatment of acute myeloid leukemia. The company has partnerships with Roche, Bristol-Myers Squibb, GlaxoSmithKline, Cephalon, and other leading organizations. For more information, please visit www.ambitbio.com.

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