An investigation into pharmaceutically relevant mutagenicity data and the influence on Ames predictive potential.

ABSTRACT:

Background

In drug discovery, a positive Ames test for bacterial mutation presents a significant hurdle to advancing a drug to clinical trials. In a previous paper, we discussed success in predicting the genotoxicity of reagent-sized aryl-amines (ArNH2), a structure frequently found in marketed drugs and in drug discovery, using quantum mechanics calculations of the energy required to generate the DNA-reactive nitrenium intermediate (ArNH:+). In this paper we approach the question of what molecular descriptors could improve these predictions and whether external data sets are appropriate for further training.

Results

In trying to extend and improve this model beyond this quantum mechanical reaction energy, we faced considerable difficulty, which was surprising considering th

SUBMITTER: McCarren P 

PROVIDER: S-EPMC3277490 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature