Event Description: Nitrosamines pose serious cancer risk in environment, food and as impurities in drugs. However, it is a difficult task to determine potency of untested nitrosamines. Lack of adequate in vivo and in vitro carcinogenicity assay data is certainly a major challenge, but at the same time, carcinogenicity risk ofNitrosamines is considered to be related to their mutagenicity, metabolic profile, and physicochemical properties. Therefore, computational approaches are becoming a potential technique to relate structural features with carcinogenic potency.
In this session we will discuss research efforts in MultiCASE to develop databases, novel algorithms, and computational tools to handle this problem.
We have developed an analog based algorithm using structural environment of the nitrosamine functionality, i.e., local similarity. A special molecular fingerprint was developed which enables retrieval of relevant analogs, and gives indication of the carcinogenic potency of the query compound when combined with physicochemical properties and experimental carcinogenic potency of the analogs. We will discuss the merits and limitations of this approach and possible factors for consideration during expert review.
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Event Description: For 25 years, MultiCASE has developed cheminformatic tools for evaluating toxicity and metabolism potential for chemicals.  Throughout that time, the MultiCASE ICH M7 Suite has become a robust collection of models and tools available to perform ICH M7 compliant risk assessments.  In accordance with the ICH M7 guideline, both expert rule-based and statistical (Q)SAR methodologies are required to assess the DNA reactivity potential of a query chemical. Each (Q)SAR methodology produces an individual outcome related to the mutagenic potential of the impurity/query chemical. In some cases the individual model outcomes conflict with each other demanding further expert review to determine the overall classification. The MultiCASE Konsolidator tool provides a unique solution to settle conflicting calls from individual models used for ICH M7.  This session will explore how the Konsolidator tool augments the expert review process to reach a better and informed decision for ICH M7 class assignment and regulatory submission.
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