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Routes to predict DILI in 2D and 3D cell cultures: developing strategies for discovery toxicology

Abstract

Drug induced liver injury (DILI) is a major health issue and contributor to the attrition of novel compounds during development. Toxicology and clinical safety have been highlighted as the major causes of project closures during preclinical and phase I drug development, with the liver identified as a major organ system (Kramer 2007; Cook, 2014). Earlier and concurrent assessment to identify and ideally predict safety concerns in drug discovery can enable better design and selection of candidate molecules. However, whilst the ability to predict safety earlier in the drug development process is clearly desirable, are existing techniques and assay cascades capable of identifying complex and previously undetectable liabilities and can we develop more predictive screens with advanced cell culture techniques?

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