Metabolites in safety testing (MIST)

Related services

• Toxicity and safety models
• CYP identification, inhibition and induction
• Metabolite identification and stability
• Pre-clinical pharmacokinetics
• ONTOMINE - In silico bioactivity, adverse effect and toxicity screening for small molecules and metabolites
• ONTOMINE ADME - In silico models for logP, logD, logS, pKa

Unexpected toxicities and safety issues are a major cause of attrition in preclinical and clinical drug development programs. Identification of the small molecule parent drug’s metabolites in human and assesing their safety comprises an important step in evaluation of the lead compounds acceptance for further development. Whilst the parent drug is to be tested in various animal in vivo as well as in vitro toxicity and safety models, its metabolites may need to be tested for toxicity as well. This can be due to possible differences in metabolic profiles between humans and used animal species.

These differences can be either presence of unique metabolites in humans compared to the used animal species or disproportionally higher presence of the metabolites may significantly differ in humans from those occuring in the used animal models. The importance of preclinical MIST is also explained in FDA Guidance to the Industry document, 2008. The key aspect of this guidance relates to the testing of the possibly differing metabolites in various species for safety using the various in vitro and in vivo tests.

We offer our customers with a comprehensive MIST package, starting from the identification of the metabolites and their stabilities in several species with in vitro and in vivo settings. The identified metabolites are first analyzed by our in sillico methods for safety risks and followed by synthesized differing metabolites and their safety and toxicity testing in various in vitro and in vivo platforms.

Please follow this link to retrieve a detailed fact sheet of the MIST package.

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Decision tree for MIST according to FDA Recommendation for the Industry, 2008.