High Content Toxicology: CellCiphr™ Hepatotoxicity Profiling

• Hepatotoxicity is one of the main reasons for drug withdrawals, accounting for 37% of all drugs withdrawn between 1994 and 2006.¹

• Drug toxicity is typically a combination of multiple mechanisms. A single experimental approach is unlikely to be predictive of the complexity involved in cellular toxicity.

• High Content Screening uses automated fluorescence imaging to simultaneously analyse multi-parametric indicators of cellular toxicity. It can detect general cell death and/or mechanisms of cell death and can cover a wide spectrum of cytopathological changes.^2,3

• The CellCiphr™ hepatotoxicity profiling assay assesses a panel of 8 key toxicity markers in primary rat hepatocytes:
• Cell Loss
• DNA Fragmentation
• Nuclear Size
• Apoptosis
• Steatosis
• Phospholipidosis
• Mitochondrial Function
• DNA Damage Response

• Using Cyprotex’s extensive database of in vitro profiling and in vivo toxicity data, the CellCiphr™ Classifier system can rank and classify unknown compounds against known toxic effects, allowing the prediction of organ toxicity.

• For drug-discovery programs using CellCiphr™ toxicity profiling to filter out toxic compounds at the start of the hit to lead stage, Cyprotex projects a saving in direct costs of over $91million. For programs using CellCiphr™ to selectively advance compounds with reduced risk of attrition due to toxicity, Cyprotex projects a $35 million increase in value for the typical clinical pipeline.