ToxTracker – the better genotoxicity assay

This is the first blog in a series to come to share what we are doing at Toxys and to inspire you. Toxys provides innovative in vitro toxicity screening solutions to rapidly identify hazardous and potential carcinogenic properties of novel compounds during the early phases of product and drug development. Toxys exclusively offers ToxTracker, a stem cell-based reporter assay for carcinogenicity hazard identification. In this first blog about our lead product ToxTracker, I will share why our customers have decided to use the ToxTracker assay and what are the unique features of the assay. Let me start with the most important thing, why our customers use the assay – because this is why our company exists.

Why our customers use ToxTracker

Our primary customers are from the pharmaceutical, chemical and cosmetics industry that are looking for better ways to determine if their novel drugs or products are safe for humans. There are generally three types of reasons (and usually it is a mix of these) why customers choose ToxTracker. First they want to screen their new compounds to make a selection which ones have the highest potential for further development and to predict results in the regulatory batch of assays, secondly they had conflicting results in the standard battery of assays (for example Ames negative, micronucleus positive) and would like get insight into the toxic mode of action to understand results and see if there is potential to rescue the compound and thirdly because they would like to have insight into the mode of action of the compound.

Next to the application of the assay, customers often indicate that they value the expertise found at Toxys and the extensive reports that allows them to understand results and make decisions on their compounds. We work in dedicated teams which are used to thinking along and shift gear as required by our customers and act as an extension of your scientific team. We offer unique expertise in toxicology and the low overhead keeps costs down.

ToxTracker uniquely offers insight into the toxic mode of action

Toxtracker is a state-of-the-art stem cell-based reporter assay that provides mechanistic insights into the primary reactive properties of novel compounds. The assays has been developed to detect various potentially carcinogenic properties of compounds. ToxTracker consist of 6 reporter cell lines each containing a unique fluorescent biomarker that allows detection of induction of DNA damage, oxidative stress, protein damage and general cellular stress. By using these 6 reporter cell lines, we are able to combine different endpoints in one assay, separate the major mode of action and sheds light on how these contribute to the cytotoxicity of compounds. By providing insight into the toxic mode of action, ToxTracker is often able to predict why compounds might give certain results in the standard battery of assays. The extensive validation of the assay with hundreds of compounds indicate that the assay is an excellent predictor of the results in the regulatory in vitro assays. ToxTracker is generally also able to predict whether compounds will be mutagenic, will give rise to micronuclei or have an aneugenic mode of action in the in vivo assays.

There are several key advantages reported by our customers in using this assay:

• the assay requires low amounts of compound, which especially in early drug development when small amounts are available is a big advantage
• our turnaround time for a report is quick – usually it takes between 1 and 2 weeks to get a report, enabling quick decision making
• extensive report that provides detailed description of the toxic mode of action and thus provides different information than the standard battery of assays.

Its place in genotoxicity assessment

During compound development, whether this is a chemical entity or pharmaceutical, compounds need to be tested for potential risks for human health. Genotoxicity testing is a crucial part of this early safety screening. The battery of in vitro genotoxicity assays that is currently available generally has an acceptable reliability to predict the potential carcinogenicity hazard of compounds, however occasionally suffers from misleading positive test results and lacks the ability to provide insight into their mode of action. Understanding of the mechanisms of toxicity is crucial to understand whether results are misleading positive.

The standard battery of in vitro genotoxicity tests usually includes the Ames bacterial mutation test and Micronucleus or chromosome aberration test. Especially the latter assays have a relative high frequency of misleading positive test results which can result in unnecessary discarding of promising compounds.

Depending on the strategy of the customer, the assay is usually applied either as an early screening tool before (the more expensive) regulatory assays or to assess the compounds mode of action because it showed unclear results in the regulatory assays (for example Ames negative, micronucleus positive).

What can we do for you?

We work together with various types of customers ranging from very small to very large companies from different industries like pharmaceutical, chemical and environmental. In our experience so far we have noticed that the assay is applied by our customers for many different reasons. The strategy in genotoxicity testing varies widely between companies and in different industries. I believe that the best way to provide you with some insight into how the assay is used is by sharing example projects – of course without company names and exact details because of confidentiality – so we plan to do this in next blogs. If you cannot wait to hear about the applications or if you want to know how our assay might be applied for your compounds and questions please feel free to contact me at p.vanrossum@toxys.com.