Assessing Preclinical Toxicity Data with Gene Expression Analysis

Drug discovery is a process of attrition and the number of drug failures far exceeds the number of successes. Recent studies have highlighted the root causes of failure: lack of efficacy is foremost and mechanism-based toxicity is close behind.

Many drugs experience these failures late in the development process—and the later the failure, the greater the cost. In the preclinical stage, the ability to determine the relevance of toxicity data to humans can help drug developers advance or eliminate early-stage compounds with greater confidence. Pharmaceutical companies can also reassess and perhaps rescue drugs that had been previously (or unnecessarily) abandoned.

Measuring drug-induced changes

For companies that need assistance in this area, CXR Biosciences is offering an investigative toxicology service based on transcriptional profiling. This technology provides a broad view of drug-induced effects by measuring changes in mRNA expression levels following exposure to chemical compounds. This application of gene expression analysis enhances the ability to determine if preclinical data is relevant to man. If the analysis shows that the reported toxicity is irrelevant, then viable compounds can be developed with greater confidence.

We're highlighting CXR because it has achieved designation as an Agilent Certified Service Provider. Our certification process requires that company personnel be trained and tested on the six major elements of Agilent's microarray platform:

• High-content 60-mer oligo microarrays printed with SurePrint technology
• Well-tested protocols that span sample isolation to hybridization
• Precise RNA quality analysis using the Agilent 2100 bioanalyzer and RNA LabChip kits
• Efficient two-color labeling using proven reagent kits and protocols
• High-sensitivity scanning and feature extraction via the Agilent microarray scanner and Feature Extraction Software
• Advanced data analysis that leverages applications such as the well-respected Rosetta Resolver^® gene expression data analysis system

These powerful tools complement CXR's skill in reducing the late-stage attrition of compounds in the development pipeline. Ultimately, reducing this rate of attrition can improve the cost effectiveness of drug discovery.

Providing specialized services and solutions

Designation as an Agilent Certified Service Provider validates a company's ability to provide high quality microarray processing and data analysis using our entire microarray platform. The Certified Service Provider program combines the provider's focused expertise with Agilent's proven products to create specialized services or complete solutions our customers can rely on to enhance their work.

In the fields of target validation and drug discovery, ExonHit Therapeutics, Icoria, the Institut Gustave-Roussy and Memorec/Miltenyi Biotec have also earned Agilent Certified Service Provider status. As more companies achieve this designation, we will work with them to find new ways to accelerate our customers' work in specialized applications.

For more information

To learn more about Agilent's printed microarray solutions, please visit the DNA Microarrays section of our Web site. For information about other Agilent life sciences products and resources, please return to the Life Sciences/Chemical Analysis main page.

Rosetta Resolver is a U.S. trademark of Rosetta Inpharmatics