WHY ToxFX? Safety is the single largest reason that drugs fail in the clinic. Toxicogenomics is rapidly becoming a standard tool for early detection of safety issues during the discovery phase in pharmaceutical research and development. As pioneers in this technology, Iconix and Affymetrix have worked together to develop the ToxFX Analysis Suite to create an easy-to-use and rapid assay for assessing compound safety. Some of the ways that ToxFX can help you are:
The Main Reasons Drugs Fail in Development
ToxFX provides contextual analysis of your data The key to accurate, value-added interpretation of gene expression data is to interpret changes in the context of a large reference dataset. A reference database allows the user to correlate observed differential gene expression with real, measured biological endpoints. ToxFX makes extensive use of the contextual information in DrugMatrix®. DrugMatrix is populated with the results of thousands of gene expression studies in which rats were systematically treated with a broad range of approved drugs as well as toxicological and biochemical standards.
Each treatment In DrugMatrix® is combined with:
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Comprehensive histopathology
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Clinical pathology data
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Drug target binding and enzyme inhibition data from a panel of 130 in vitro
pharmacology assays
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Extensive literature curation
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Extensive biological pathway information to anchor gene expression changes to phenotypic endpoints
DrugMatrix is the world’s largest source of these reference data. Iconix informatics scientists have systematically mined these expression data coupled with the toxicologic and pharmacologic endpoints to uncover Drug Signatures® -- patterns of expression changes -- that are used as statistically validated biomarkers. Drug Signatures link the expression pattern of groups of genes to key toxicological and pharmacological endpoints and are a user-friendly distillation of the complex, multi-dimensional data contained in DrugMatrix. Drug Signatures can diagnose and predict specific off-target effects and toxicological reactions in different organs and tissues, which help to identify and explain specific mechanisms of toxicity and compound activity.
ToxFX provides an automated analysis for dramatic time savings in data interpretation Pharmacologically active compounds can alter the expression levels of hundreds or thousands of genes. It is laborious and time-consuming to extract and understand which of those changes are meaningful and may relate to compound toxicity and pharmacology. The ToxFX Analysis Suite automates these tasks and generates a report within minutes of large-scale data submission. The report provides a clear picture of potential safety issues. It also includes definition of the genes that are likely to be most relevant to the observed toxicity and/or pharmacology as well as the biological pathways that are most likely to play a role in the observed toxicity. These results empower decision-making immediately rather than the weeks or months that it takes to receive a standard pathology report. ToxFX accomplishes this by application of the vast contextual information contained in DrugMatrix as well as through application of the highly validated DrugSignatures that have been developed from this reference data set.
Focused ToxFX arrays support compound screening approaches Iconix and Affymetrix have collaborated to design a customized GeneChip array for exclusive use with the ToxFX Analysis Suite. This is a sub-array containing 2072 probe sets with the same feature size and probe set size as the proven Affymetrix GeneChip Rat Genome 230 2.0 array. The content of the array is based on those probe sets that the DrugMatrix reference database indicates are most informative from a toxicology perspective. These include the complete set of genes involved in 22 key toxicology pathways and 55 Drug Signatures, as well as a set of genes that toxicologists widely agree are vital to the understanding of toxic responses in rat liver, heart and kidney.
