In vitro chemical safety assessment often relies on simple and general cytotoxicity endpoint measurements and fails to adequately predict human toxicity. Cellular and animal models often report only on toxicological effects without elucidating chemical mode of action (MOA). This necessitates follow up investigations and delays candidate development. As a solution, ToxProfiler, a human based New Approach Method (NAM), has integrated GFP reporters into human derived hepatocytes to identify toxicologically significant pathway activation via high content imaging in 384-well plates.

By simultaneously measuring 7 different stress responses, quantitative points of departures (PoDs) are used to construct a unique ToxProfiler fingerprint that when combined with pharmacokinetic data, identifies in vivo relevant toxicities such as drug-induced liver injury (DILI). The fingerprint can also be used to identify MOA, rank compounds, and be applied in early phases of safety assessment with <5 mg of compound. By exploiting glucose deficient media, ToxProfiler MAX also identifies mitochondrial toxicants.

In this webinar, we will illustrate how ToxProfiler can be applied to generate a toxicological signature for compounds. These signatures can be compared to a database of reference compounds to predict the specific toxicological properties of unknown substances. We will show how ToxProfiler can be used to accurately predict mitochondrial toxicity. In addition, we will demonstrate how ToxProfiler-derived PoDs and human cMAX information can be applied to assess the ToxProfiler assay performance for the classification of DILI. DILI is a leading cause of clinical trial failure, and it accounts for 30% of market withdrawals.

Would you like to learn more about ToxProfiler and the applications for investigative toxicology? Join us in our webinar!

Presentations:

dr. Bas ter Braak – Study Director at Toxys

Prof. Bob van de Water – Professor Drug Safety Sciences at LACDR, Leiden University

During this webinar, participants will learn:

• How the ToxProfiler assay works.
• How the ToxProfiler assay can be applied for mechanistic toxicity testing.
• Specific applications of ToxProfiler to predict mitochondrial toxicity
• How the ToxProfiler assay can be applied for predicting DILI.