ArticleToxicology research2025
Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates.
Article in Toxicology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Interest in inhibiting target proteins through covalent binding mechanisms has increased in the last decade due to the potential for beneficial pharmacological properties. However, the inherent targeted covalent inhibitor (TCI) adverse off-target reactivity risk requires a mitigation strategy early during drug discovery. The aim of this research was to design a pre-clinical hepatic safety assessment strategy for TCIs considering risk associated with electrophilic warhead reactivity and reactive metabolites formation at clinically-relevant plasma concentrations. The mitigation strategy was applied to compound 35, a potent irreversible inhibitor to KRAS
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