Lhasa Limited is pleased to announce the release of Nexus 2.5, which incorporates new Derek Nexus knowledge relating to skin sensitisation, and updates to the Sarah Nexus training set to enable informed decision making on chemical safety.
Below is a summary of some of the new and improved program features you can expect to see within this release…
New endpoint in Derek Nexus predicts strong/extreme sensitisers
A new endpoint has been introduced to Derek Nexus 2022 1.0, Skin Sensitisation High Potency Category (HPC). This endpoint contains alerts describing a skin sensitisation HPC, consisting of a set of structural features within a mechanistic domain which are likely to be associated with extreme skin sensitisation potential in the Local Lymph Node Assay. The presence or absence of alerts for skin sensitisation HPC provides information about which of the Dermal Sensitisation Thresholds (DSTs) is the most appropriate to use.1
Donated Ames mutagenicity data utilised within new Sarah model
A new Sarah Nexus model has been built called “Sarah model – 2022.1”, which uses Ames mutagenicity data from an expanded training set of 12,195 compounds sourced from data contained in the Vitic database and donated by Lhasa Limited members. The chemical structures of the training set compounds have been standardised and the biological data curated to reach an overall Ames result for each data point. This produces a self-organising hypothesis network (SOHN) model containing 398 hypotheses (305 unique).
N-nitroso compound arguments added to ICH M7
To enhance expert review assessment support, Nexus alerts the reviewer when a compound is in the “cohort of concern”. This allows users to limit the use of mutagens that display extremely high carcinogenic potency (cohort of concern) to lower levels of acceptable intake as defined in the ICH M7 guidance. In Nexus 2.5, 5 new arguments have been implemented to specifically discuss subclasses of N-nitroso compounds for which structural features are expected to reduce the mutagenic potential as discussed in the related Derek alert 007. These have been implemented with either a “Positive”, “Negative” or “Inconclusive” overall in silico call.
If you would like more information on Nexus 2.5, contact our Applied Sciences Team.To discover all features and benefits of Nexus 2.5, software users can access the full release notes here.
References
- Chilton et al, Regul Toxicol Pharmacol (2022), submitted.