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Aldehyde oxidase is a metabolic enzyme with species differences in expression. SGX523, a reported substrate of aldehyde oxidase, failed in the clinic due to acute renal failure caused by an insoluble metabolite, which was unexpected due to acceptable safety in rat and dog. The liver humanized PXB-mouse® was employed to assess the suitability of this model for recreating the acute renal effects of SGX523. An integrated approach assessing metabolism, exposure in the target tissue, renal injury biomarkers, and histology will be described.
Watch the on-demand webinar to learn:
- The importance of identifying biotransformation mechanisms, and species differences associated with metabolic enzymes such as aldehyde oxidase.
- How to integrate drug metabolism information early within a safety assessment program to ensure the right species are selected to assess tolerability of drug candidates.
- How to assess the suitability of the liver humanized PXB-mouse® model into a safety assessment program associated with metabolite-mediated acute renal toxicity.
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