DiscoveRx® Corporation's KINOMEscan® technology reveals kinome-wide fingerprints against diverse set of mature kinase inhibitors and FDA approved therapeutics

Release date: 11/16/2011

Fremont, US - November 16, 2011 - DiscoveRx announced today the release of the most detailed comprehensive assess­ment of interaction profiles of known kinase inhibitors across the kinome published to date in the November 2011 issue of Nature Biotechnology, titled “Comprehensive analysis of kinase inhibitor selectivity.”  This seminal publication utilizing the KINOMEscan platform, wholly-owned by DiscoveRx Corporation, in collaboration with Ambit Biosciences®, quantitatively assessed the interaction patterns of 72 kinase inhibitors against 442 kinases, and included all major kinase groups plus a panel of 54 clinically relevant mutants and several activation state-specific ABL assay pairs.  This work expands on their 2008 research publication, recently hailed by Nature Biotechnology as one of the most cited research publications during the period 2006 to 2011.

In addition to providing a quantitative assessment of near-complete coverage of the human protein kinome against a diverse set of chemical scaffolds, this dataset provides a true measure of compound potency, with thermodynamic binding constants reported for each identified interaction.  Co-senior author Patrick Zarrinkar notes: “this study reveals that for a majority of the primary, intended kinase targets of the inhibitors tested, at least one selective compound has been identified, and we are thus optimistic that a majority of kinases can be targeted by selective inhibitors”.  In addition, a large number of previously undescribed activities of known inhibitors were identified, suggesting new applications for known drugs and starting points for the development of optimized inhibitors targeting novel kinases.  2009 Lasker award winner and targeted therapy pioneer Nicholas Lydon comments: “this comprehensive dataset provides an invaluable resource to the drug discovery community, and will facilitate the pharmacologic validation of putative novel kinase targets identified by cancer genomics approaches such as deep sequencing and siRNA campaigns”.  This study also systematically explored the impact of inhibitor binding mode on kinome-wide selectivity, and according to co-senior author Daniel Treiber, “inhibitors that target unusual or inactive kinase conformations are generally most selective, but there are important exceptions, and type I inhibitors often exhibit impressive overall selectivity and relative selectivity for the intended target”.  This publication, including supplemental data tables and interactive TREEspot compound/kinase visualization maps for all 72 compounds is available at: www.kinomescan.com/References/Comprehensive-analysis-of-kinase-inhibitor-selectivity

About DiscoveRx Corporation
Founded in 2000, DiscoveRx is a privately held, venture-backed company headquartered in Fremont, California, with an additional office in Birmingham, England. The Company pioneered the use of β-galactosidase enzyme fragment complementation in biochemical and cell based assays for discovery research, and holds extensive intellectual property in this area. DiscoveRx is dedicated to the development and commercialization of innovative solutions to study GPCRs, Kinases and other major drug target classes, and many of their innovative products have been widely adopted in pharmaceutical and biotech drug screening laboratories worldwide. The Company is also a recipient of two Frost and Sullivan 2008 awards: Award for Innovation in North American Healthcare Market as well as a European Product Line Strategy Award for it's GPCR Cell Based assay portfolio. For more information on DiscoveRx products, please visit www.discoverx.com.

About KINOMEscan® Platform
KINOMEscan, now part of DiscoveRx, is a leading provider of kinase inhibitor profiling services to the kinase drug discovery industry. The KINOMEscan screening platform employs a novel and proprietary active site-directed competition binding assay to quantitatively measure interactions between test compounds and more than 450 kinase assays and disease relevant mutant variants. This robust, reliable and flexible assay technology affords investigators the ability to extensively annotate compounds with accurate, precise and reproducible data, and is accessible through a variety of flexible screening solutions including single target HTS, personalized assay selection for custom panels and a growing portfolio of investigative tools to elucidate compound mechanism of action.

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