Drug discovery is a long term process (typically more than 10 years) and is expensive (more than £600 million per drug developed).
Large numbers of potential drug compounds have been created by combinatorial chemistry, but the current high throughput screening process to try and sift out the candidates has provided data which appears to be unreliable as a predictor of what will happen in the clinic. As a result there are many late stage failures and a high level of attrition in the drug development pipeline from unexpected toxicity.
Although in vitro screening tests can be sensitive or specific, it appears almost impossible to combine both these desirable features. There are many factors involved, one of which is the lack of metabolic activity on the cells that are used in the in vitro models. Even if healthy human cells are used – and such cells are very difficult to source – they are frequently cultured in a static environment where the key genes (e.g. CYP genes in hepatocytes) are down-regulated and hence the important enzymes responsible for drug metabolism are not active.
The Kirkstall Quasi Vivo® system, with its media flow system, has been shown to restore the function of cells or tissue even after activity has been switched off by unfavorable conditions or storage by freezing.
Evidence from several trials has now established the clear benefits of Quasi Vivo®for in vitro testing of drug toxicity or ADME/PK studies:
- Liver Cells exhibit physiologically relevant levels of CYP P450 activity leading to correct metabolic function (Phase I, Phase II) and xenobiotic transcription factors and transporters.
- Tissue and barrier models (gut, skin, and blood-brain) can be constructed with the modular QVS chambers facilitating ADME/PK studies.
- Long term cell culture is possible for studying repeated dose toxicity or efficacy of therapy.
- Models are physiologically relevant (co-culture and tissue-like constructs) to improve understanding and prediction of clinical observations.
- Transporter assays are feasible.
Contact our application specialists at email@example.com to find out more about how Quasi Vivo® can help with your research or the development of more predictive assays.
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