In March 2012, Cyprotex presented a poster on their CellCiphr® research. The study focused on using a PBPK (physiologically based pharmacokinetic) modeling approach to estimate exposure, combined with CellCiphr® high content screening data for a panel of mechanistic toxicity endpoints, to greatly increase the predictive power for the determination of safety risk. |
The rapid expansion of HCS technology throughout the pharmaceutical industry and academic research centers validates the usefulness of the information-rich screening approach.
2Zanella F, Lorens JB and Link W (2010) Trends Biotechnology 28(5); 237-245
Instruments | Cellomics ArrayScan® VTI (Thermo Scientific) |
---|---|
Analysis Method | High Content Screening with CellCiphr® Classifier System |
Cell Types | HepG2 (replicating) and primary rat hepatocytes (metabolically competent) |
Toxicity Markers | Extended panel of toxicity markers including: Apoptosis Cell cycle arrest Cell loss Cytoskeletal disruption DNA fragmentation and damage response Glutathione depletion Mitochondrial function Mitosis marker Nuclear size Oxidative stress Phospholipidosis Reactive oxygen species Steatosis Stress kinase activation |
Test Article Concentration | 10 point dose response curve in duplicate |
Data Delivery | CellCiphr® toxicity report including: AC50 Safety ranking Safety alert Heat maps (normalized to Cmax if available) |
CellCiphr® Toxicity Profiling Report | Sensitivity | Specificity |
---|---|---|
HIAT Method3 | 35% | 100% |
CellCiphr® Premier | 70% | 100% |
1 Dykens JA and Will Y (2007) Drug Discovery Today 12; 777-785
2 Zanella F et al., (2010) Trends Biotechnol 28(5); 237-245
3 Xu JJ et al., (2008) Toxicol Sci 105(1); 97-105
Learn more about toxicology in our popular Mechanisms of Drug-Induced Toxicity guide
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