Clustering and its application in multi-target prediction.
Drug discovery teams are beginning to apply non-screening techniques to make early associations between chemical structure and various biological and druggability characteristics of compound series. The increasing availability of multiple data sets and models of target potency, ADME characteristics, and toxicity allows a researcher from any discipline to draw quick associations with multiple endpoints on sets of compounds or chemical scaffolds. Cluster analysis, for instance, can be used to correlate screening potency with data predicted from both freely available and commercially available models. In the future researchers will be able to draw chemical-biological associations 'on-the-fly' using various clustering or similarity techniques to determine whether the proposed toxicity of a drug is related to its chemical structure or its proposed efficacy mechanism. In this review associations are illustrated with target potency data gleaned from the literature associated with CYP450 substrate predictions from GeneGo's MetaDrug.
Liu
William
W
University of California at Berkeley, Department of Nutritional Science & Toxicology, CA 94720-3104, USA. will.c.liu@gmail.com
Johnson
Dale E
DE
D016000:Cluster Analysis; D019295:Computational Biology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D004345:Drug Industry / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity; D014116:Toxicology
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System