Toxicology biomarkers are structural or functional measurements that correlate with an adverse change in the physiology of an organism. A familiar example is elevated serological alanine aminotransferase (ALT) activity as a biomarker of hepatic injury. Toxicology biomarkers such as ALT help us select compounds with desirable margins of safety in the lead optimization (LO) phase of drug development, and allow us to identify target-organ toxicities that should be monitored in patients during clinical drug development. Unfortunately, useful clinical and pre-clinical biomarkers are not available for many compound-induced pathologies. Promising new molecular techniques that can address this gap by finding candidate biomarkers include genomics, proteomics, and metabonomics. Successful application of these technologies to develop toxicology biomarkers could increase the quality and number of clinical candidates selected during LO, and improve our ability to monitor drug safety in patients. In this chapter we present a case history using toxicogenomics in which DMBT1 was developed as a transcriptional biomarker of bile duct hyperplasia induced via oval cell proliferation, a toxicologic pathology for which biomarkers are needed.

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