Adverse outcome pathways

Bolt, Hermann M.

doi:10.1007/s00204-017-2123-6

Cited by 3 publications

(2 citation statements)

References 20 publications

(17 reference statements)

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“…The concept of adverse outcome pathways (AOPs) was proposed by the Organisation for Economic Co-operation and Development (OECD) as a way to clearly define known mechanisms of toxicity. 245 AOPs start with an initiating molecular event and result in a subsequent chain of resulting events at various stages of organization, culminating with an adverse effect to the organism. 245 By defining AOPs in this way, they are amenable to computational modeling, which is an ultimate goal of the process.…”

Section: Discussionmentioning

confidence: 99%

“…245 AOPs start with an initiating molecular event and result in a subsequent chain of resulting events at various stages of organization, culminating with an adverse effect to the organism. 245 By defining AOPs in this way, they are amenable to computational modeling, which is an ultimate goal of the process. 246 From a regulatory and showing relationships between data that can be integrated to combine complementary data sets that provide a more complete picture of drug-related effects.…”

Section: Discussionmentioning

confidence: 99%

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Screening Strategies and Methods for Better Off-Target Liability Prediction and Identification of Small-Molecule Pharmaceuticals

et al. 2019

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Pharmaceutical discovery and development is a long and expensive process that, unfortunately, still results in a low success rate, with drug safety continuing to be a major impedance. Improved safety screening strategies and methods are needed to more effectively fill this critical gap. Recent advances in informatics are now making it possible to manage bigger data sets and integrate multiple sources of screening data in a manner that can potentially improve the selection of higher-quality drug candidates. Integrated screening paradigms have become the norm in Pharma, both in discovery screening and in the identification of off-target toxicity mechanisms during later-stage development. Furthermore, advances in computational methods are making in silico screens more relevant and suggest that they may represent a feasible option for augmenting the current screening paradigm. This paper outlines several fundamental methods of the current drug screening processes across Pharma and emerging techniques/technologies that promise to improve molecule selection. In addition, the authors discuss integrated screening strategies and provide examples of advanced screening paradigms.

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Section: Discussionmentioning

confidence: 99%