Carcinogenicity assessment with Kaptis

Supporting accurate and cost-effective carcinogenicity risk assessment

Determine the carcinogenic risk of your compound, using adverse outcome pathways (AOPs) to organise knowledge
Reach a decision in your weight of evidence (WoE) assessment quickly, using an alternative approach for carcinogenicity assessments
Save money in your compound discovery costs and shorten development timelines by 2-3 years, bringing vital drugs to market faster

Moving towards non-animal new approach methodologies (NAMs)

Within many sectors of the life sciences industry, animal testing is still considered a primary option for toxicity testing, and as a result is used heavily. The limitations of this model are now well understood and non-animal new approach methodologies (NAMs) present an ideal opportunity to improve on the traditional approach.

But how do you overcome the challenges in validation, combining results and understanding NAMs?

By using adverse outcome pathways (AOPs) to organise this knowledge, the following questions can be answered:

Given this compound and/or this assay result, what adverse outcome (AO) is a cause for concern?

Given this predicted AO, what assay should I run next?

Kaptis uses AOPs to support you in answering these questions, to determine the carcinogenic potential of your compound

Our carcinogenicity AOP knowledge framework in Kaptis has been created, curated and peer reviewed by our expert Lhasa scientists. This framework enables you to quickly reach a decision in your weight of evidence (WoE) assessment.

In some cases, for example in line with the recently published ICH S1B guidelines, it is possible to avoid running a full carcinogenicity animal study, where the WoE assessment clearly shows that it would add no value to the overall assessment.

Derek Nexus highlights

Access over 40 years of expert Structure-Activity Relationship (SAR) knowledge for the carcinogenicity endpoint
Derek contains well-established Structure-Activity Relationship (SAR) knowledge for the carcinogenicity endpoint. The SAR knowledge is derived from both public and proprietary member data sources and is updated as new data becomes available.

Identify any toxicophores highlighting possible carcinogenic hazard
Assess your compounds against key toxicity endpoints in relation to expert derived toxicophores. The expert comments associated with a Derek Nexus alert can help you to decide if this compound structure is a concern or not.

Understand the SAR behind carcinogenicity predictions
The scientific comments which accompany a Derek Nexus alert will describe the alert mechanism of action.

The Lhasa Carcinogenicity Database (LCDB) is a significant source of long-term carcinogenicity studies and can help you to understand if there is existing data available for your compound.

LCDB highlights

Access actively maintained public carcinogenicity data for free
The data within the LCDB is presented within a user friendly and standardised interface. We continuously update the database, as new data becomes available. The LCDB was founded in 2016 on the now retired Carcinogenic Potency Database (CPDB), created by Lois Gold and her team. The database is free for everyone to access.

View TD50 values which can help you to calculate acceptable intakes
TD50 values are an important aspect of any carcinogenicity assessment. TD50 values indicate the lifetime dose at which tumours would be observed in 50% of animals, for a given compound, which otherwise would have remained tumour free without dosing. There are two TD50 values in the LCDB; Lhasa TD50 and CPDB TD50. We have calculated the Lhasa TD50 values based on the values provided by Lois Gold and her team, producing a transparent methodology for calculating TD50 values from experimental data, in a manner consistent with the CPDB. Displaying both TD50 values in the LCDB has enabled validation of the calculation method by comparison with the original CPDB values. As we expand the LCDB data set, we now also calculate TD50 values for the newly added data.

Find similar analogues using substructure or similarity searches
Where there is not an exact match for your compound in the LCDB, you can make use of the substructure or similarity search functionality – which can be used to help define the acceptable limit.

Vitic is a source of high-quality, peer-reviewed public and proprietary carcinogenicity data. When used alongside the LCDB, Vitic can help you to understand if there is existing data available for your compound.

Vitic highlights

Access high-quality public and proprietary data
The data within Vitic is expert-curated, high-quality, peer-reviewed data from both published and unpublished sources.

Search for data within other related endpoints
Alongside carcinogenicity data, you can also search for data within other related endpoints such as mutagenicity and chromosome damage, which can help to build your understanding of a carcinogenic risk.

Find similar structural analogues using substructure or similarity searches
Where there is no exact match within Vitic, you can make use of the substructure or similarity search functionality.

Related publications

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Which carcinogenicity study should I use? Automated identification of reliable studies

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Ames Concordance with the In Vivo Transgenic Rodent (TGR) Gene Mutation Assay for NDSRIs and Relative In Vivo TGR Potency with Nitrosamines with Robust Dose-Response Carcinogenicity Data

Poster

Can the Second Species Be Replaced by an Adverse Outcome Pathway-Based In Silico Model?