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Drug development is a long, expensive and risky process. It's known that of the 250 compounds entering pre-clinical testing, 10 will enter clinical trials but only 1 will be approved. It's also known that since the 1990's more than half of new drug applications failed due to unpredicted toxicity effect and this trend is expected to continue as the pharmaceutical industry and regulatory agencies shift the risk-to-benefit ratio toward increasing emphasis on drug safety.
Cellumen developed a cellular systems biology approach to give biopharmaceutical researchers the means to screen compounds for broad-ranging toxic effects early in the drug discovery process using tissue-specific cell models. CellCiphr™ Cytotoxicity Profiling uses a combination of toxicity-relevant cells and toxicity biomarkers to illuminate cellular system responses to toxic challenges in a specially designed set of CellCiphr™ Cytotoxicity CSB™ Panels. These panels are selected to monitor the effects of test compounds on many cellular systems responses known to be correlated with toxic challenge, such as oxidative stress, organelle function, stress pathway activation, cytoskeletal integrity, cell cycle and DNA damage. Multiplexed cell-, feature-, time- and concentration-dependent profiles are generated using CellCiphr™ Profiles. The Classifier Analysis Tool tabulates results including the maximum tolerated dose, AC50 curves, common modes of activity, clusters with similar activity profiles, correlation of profiles to known toxic control profiles, rank order and safety risks for prioritization. The CellCiphr™ final Profiling Report is designed to identify toxic liabilities early in the drug discovery process.
Flow to compound testing and reporting using CellCiphr™ CSB™ technology
The Advantage to Using CellCiphr™ Cytotoxicity Profiling
- Cellular Systems Biology approach for deeper knowledge
- True image-based high throughput capability
- Minimal compound requirement (generally less than 2 mg)
- Proprietary data Classifier provides a tool to reliably prioritize compounds early in the development process and to gain insights into mechanisms of action
- HCS read-out allows data re-analysis and re-mining for additional cell by cell and sub-cell population analysis
Levels of information complexity using CellCiphr™ Cytotoxicity Panels. Each data point in a CellCiphr™ Profile is the result of the measurements from hundreds to thousands of cells in replicate 10 point dose-response curves at concentrations up to 100 µM. Drilling down to these data provides the most detailed level of information and understanding of compound effects on cellular and sub-cellular functions.
Profiling Report
The CellCiphr™ final Profiling Report conveniently summarizes in 2 pages:
- All 33-feature dose-response curves with best curve fit
- All AC50 calculations
- Earliest and most sensitive cell feature responses
- General measurements of cytotoxicity
- Similarity plots and correlations to compounds in a series and to control compounds
- Rank order within a group of defined compounds
- Safety Index with high correlation to in vivo toxicity
CellCiphr™ Cytotoxicity Profiling products and services are designed to identify toxic liabilities early in the drug discovery process.
