Mechanistic in vitro tox-assays
19 October 2020
In addition to assays for ADME research, Admescope’s service portfolio contains options for investigating in vitro toxicity to support internal decision making at the early stages of drug discovery and development projects. Conducting in vitro tox-assays under non-GLP conditions is a cost-effective way to identify potential issues related to hepatotoxicity, genotoxicity, and cardiotoxicity, which are the most often encountered toxicity challenges in drug development. In addition, there are also options to search for evidence about the mechanism behind the toxicity by mechanistic in vitro tox assays.
The mechanism of hepatotoxicity is often related to mitochondrial dysfunction; liver being enriched with these organelles. To evaluate this, Admescope offers the Glu/Gal MitoTox assay. In this assay, the experimental conditions force the cells to produce ATP through oxidative phosphorylation in the mitochondria. ATP content in the cells is monitored, which reveals potential mitochondrial toxicity.
Another common form of drug induced toxicity relates to increased oxidative stress, which causes cellular damage. Glutathione is one of the most important antioxidants in the body. Oxidative stress can be evaluated by measuring the ratio of reduced and oxidized forms of glutathione (GSH/GSSG), which indicates the potential oxidative stress caused by the test compound.
Apoptosis is programmed cell death, which doesn’t cause inflammatory reaction in the cells. Another form of cell death is necrosis, which is usually induced by external factors and causes an inflammatory reaction. Many of the antitumour therapies cause induction of apoptosis in the tumour cells. Induction of apoptosis can be evaluated by measuring caspase 3/7 activity, which reveals whether the cell death is due to the apoptosis or necrosis.
It may be worthwhile to remind you that we provide also assays for investigating formation of reactive metabolites, reactivity of acyl-glucuronide metabolites and inhibition of BSEP transporter. Please contact us for more information or for setting up a teleconference to discuss how we could help you!