Ex vivo Toxicology
Drug toxicity, often manifested as liver toxicity, is a key reason for xenobiotic attrition. Identifying potential toxicity at an early stage in drug, agrochemical or chemical development can save both time and developmental costs, and most importantly reduce the likelihood of late stage failure.
KaLy-Cell is the ideal partner to assist you in understanding the liver-mediated toxic liability of your compounds using a panel of different ex vivo evaluations on hepatic subcellular fractions. Our focus on state of the art techniques allow for high quality data to be generated rapidly and cost-effectively. To that end, KaLy-Cell is actively involved in several R&D projects to improve the prediction of toxicological events and allows for a better understanding of the mechanisms of drug toxicity.
- Highly reproducible, accurate data – validated and used by pharmaceutical, biotechnology, agrochemical and cosmetics companies, and academic organizations.
- Delivery of data within several weeks at reception of compounds, to fit in with the make-test timelines in drug discovery. A number of different reporting options are available.
- Attention to good quality customer care, with highly trained Scientists on hand to explain results and suggest the most appropriate experimental strategy.
- Flexibility – studies can be tailored to our customers’ specific requirements.
- Regulations – our services maintain and comply with regulatory guidelines providing constant confidence in the data.
Drug Induced Liver Injury
KaLy-Cell offers innovative ex vivo read outs of toxicity in subcellular fractions including Drug Induced Liver Injury (DILI) and a range of drug-drug interaction screens:
- Oxidative Stress – to address hepatic disorders of detoxification pathways
- Steatosis – to address hepatic lipid processing disorder, leading to accumulation of triglycerides within the liver cells.
- Changes in gene expression – using RT-qPCR or transcriptomic signature to understand toxicologically relevant changes in gene expression.
- Customized service - flexible service where we can investigate endpoints and time points in livers from different species to address particular customer issues.
Ex vivo Enzyme induction and Inhibition
- Ex vivo induction of major liver metabolic enzymes – using RT-qPCR for enzyme expression and LC/MS detection of reaction products for enzyme activities, in order to evaluate risk of drug-drug interactions or pathologies related to liver metabolism, in particular those due to inhibition and/or induction of enzymes involved in the metabolism of endogenous or exogenous compounds. They can provide the following information to your investigation:
- Which prototypical CYP inducers the xenobiotic or drug candidate resembles
- Which species most closely resembles human
- Is there a risk for drug-drug interactions
- Is there increased elimination (auto-induction)?
- Ex vivo inhibition of enzymes in subcellular fractions - LC/MS detection of reaction products for subcellular enzyme activities, cytosolic or microsomal, allow to evaluate:
- Direct inhibition of various enzymes: example inhibition of cytosolic HPPD
- Various enzyme activities after in vivo treatment – species comparison: example TAT activity.