Computational Approach to Structural Alerts: Furans, Phenols, Nitroaromatics, and Thiophenes.

ABSTRACT: Structural alerts are commonly used in drug discovery to identify molecules likely to form reactive metabolites and thereby become toxic. Unfortunately, as useful as structural alerts are, they do not effectively model if, when, and why metabolism renders safe molecules toxic. Toxicity due to a specific structural alert is highly conditional, depending on the metabolism of the alert, the reactivity of its metabolites, dosage, and competing detoxification pathways. A systems approach, which explicitly models these pathways, could more effectively assess the toxicity risk of drug candidates. In this study, we demonstrated that mathematical models of P450 metabolism can predict the context-specific probability that a structural alert will be bioactivated in a given molecule. This study focuse

SUBMITTER: Dang NL 

PROVIDER: S-EPMC5871347 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature