Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

The Use of a Chemistry-based Profiler for Covalent DNA Binding in the Development of Chemical Categories for Read-across for Genotoxicity

The Use of a Chemistry-based Profiler for Covalent DNA Binding in the Development of Chemical... An important molecular initiating event for genotoxicity is the ability of a compound to bind covalently with DNA. However, not all compounds that can undergo covalent binding mechanisms will result in genotoxicity. One approach to solving this problem, when in silico prediction techniques are being used, is to develop tools that allow chemicals to be grouped into categories based on their ability to bind covalently to DNA. For this analysis to take place, compounds need to be placed within categories where the trend in toxicity can be explained by simple descriptors, such as hydrophobicity. However, this can occur only when the compounds within a category are structurally and mechanistically similar. Chemistry-based profilers have the ability to screen compounds and highlight those with similar structures to a target compound, and are thus likely to act via a similar mechanism of action. Here, examples are reported to highlight how structure-based profilers can be used to form categories and hence fill data gaps. The importance of developing a well-defined and robust category is discussed in terms of both mechanisms of action and structural similarity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alternatives to Laboratory Animals SAGE

The Use of a Chemistry-based Profiler for Covalent DNA Binding in the Development of Chemical Categories for Read-across for Genotoxicity

Download PDF
15 pages

Loading next page...
 
/lp/sage/the-use-of-a-chemistry-based-profiler-for-covalent-dna-binding-in-the-sLbpJ8XKt1

References (16)

Publisher
SAGE
Copyright
© 2011 Fund for the Replacement of Animals in Medical Experiments
ISSN
0261-1929
eISSN
2632-3559
DOI
10.1177/026119291103900206
Publisher site
See Article on Publisher Site

Abstract

An important molecular initiating event for genotoxicity is the ability of a compound to bind covalently with DNA. However, not all compounds that can undergo covalent binding mechanisms will result in genotoxicity. One approach to solving this problem, when in silico prediction techniques are being used, is to develop tools that allow chemicals to be grouped into categories based on their ability to bind covalently to DNA. For this analysis to take place, compounds need to be placed within categories where the trend in toxicity can be explained by simple descriptors, such as hydrophobicity. However, this can occur only when the compounds within a category are structurally and mechanistically similar. Chemistry-based profilers have the ability to screen compounds and highlight those with similar structures to a target compound, and are thus likely to act via a similar mechanism of action. Here, examples are reported to highlight how structure-based profilers can be used to form categories and hence fill data gaps. The importance of developing a well-defined and robust category is discussed in terms of both mechanisms of action and structural similarity.

Journal

Alternatives to Laboratory Animals – SAGE

Published: May 1, 2011

There are no references for this article.