Referenced in: none

Automatically associated channels: Kv11.1

Title: Lead optimization using matched molecular pairs: inclusion of contextual information for enhanced prediction of HERG inhibition, solubility, and lipophilicity.

Authors: George Papadatos, Muhammad Alkarouri, Valerie J Gillet, Peter Willett, Visakan Kadirkamanathan, Christopher N Luscombe, Gianpaolo Bravi, Nicola J Richmond, Stephen D Pickett, Jameed Hussain, John M Pritchard, Anthony W J Cooper, Simon J F Macdonald

Journal, date & volume: J Chem Inf Model, 2010 Oct 25 , 50, 1872-86

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20873842

Abstract
Previous studies of the analysis of molecular matched pairs (MMPs) have often assumed that the effect of a substructural transformation on a molecular property is independent of the context (i.e., the local structural environment in which that transformation occurs). Experiments with large sets of hERG, solubility, and lipophilicity data demonstrate that the inclusion of contextual information can enhance the predictive power of MMP analyses, with significant trends (both positive and negative) being identified that are not apparent when using conventional, context-independent approaches.