Cell-Based Assays for Hepatotoxicity:
Cell-Based Assays for Hepatotoxicity: Cell-Based Assays for Hepatotoxicity:
The need for new assays and techniques to predict drug toxicity 90% of compounds fail in drug development 1 … Compounds Successfully Marketed Failed Compounds • Factors causing failure of drug candidates2 – 45% Poor ADME properties – 11% In vivo toxicity – 10% Adverse clinical effects – 28% Insufficient efficacy – 6% Commercial reasons … Resulting in an estimated $70 M spend per drug failure on ADME / Toxicity 3 1 Drug Discovery World (Summer 2005) – Conley, “High content screening: emerging importance of novel reagents/probes and pathway analysis” 2 Business Insights Report, “Predictive ADME and Toxicology Strategies” (2006) 3 D&MD Report (2007)
Inability to accurately screen for toxicity effects candidates is a key issue with current techniques. Traditional Focus for ADME/ Toxicity 1000s compounds 100s compounds
- Page 1 and 2: Cell-Based Assays for Hepatotoxicit
- Page 3: Now: High Content Analysis Automate
- Page 7 and 8: Development of a high content analy
- Page 9 and 10: Development of a high content analy
- Page 11 and 12: HepG2 cells treated with Campotheci
- Page 13 and 14: Development of high content analysi
- Page 15 and 16: Cellular Targets for Neurotoxicity
- Page 17 and 18: Assays for detecting toxicity in as
- Page 19 and 20: Detecting changes in neuronal and a
- Page 21 and 22: Assessment of toxin effects on syna
- Page 23 and 24: Preliminary data: comparison of HCA
- Page 25 and 26: Preliminary data: comparison of HCA
- Page 27 and 28: Summary Cell-based assays for hepat
The need <strong>for</strong> new assays and techniques to<br />
predict drug toxicity<br />
90% of compounds fail<br />
in drug development 1 …<br />
Compounds<br />
Successfully<br />
Marketed<br />
Failed<br />
Compounds<br />
• Factors causing failure of drug<br />
candidates2<br />
– 45% Poor ADME properties<br />
– 11% In vivo toxicity<br />
– 10% Adverse clinical<br />
effects<br />
– 28% Insufficient efficacy<br />
– 6% Commercial reasons<br />
… Resulting in an estimated $70 M spend per drug failure on ADME / Toxicity 3<br />
1 Drug Discovery World (Summer 2005) – Conley, “High content screening: emerging importance of novel reagents/probes and pathway analysis”<br />
2 Business Insights Report, “Predictive ADME and Toxicology Strategies” (2006)<br />
3 D&MD Report (2007)
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