Novel computational approaches to polypharmacology as a means to define responses to individual drugs.
Polypharmacology, which focuses on designing therapeutics to target multiple receptors, has emerged as a new paradigm in drug discovery. Polypharmacological effects are an attribute of most, if not all, drug molecules. The efficacy and toxicity of drugs, whether designed as single- or multitarget therapeutics, result from complex interactions between pharmacodynamic, pharmacokinetic, genetic, epigenetic, and environmental factors. Ultimately, to predict a drug response phenotype, it is necessary to understand the change in information flow through cellular networks resulting from dynamic drug-target interactions and the impact that this has on the complete biological system. Although such is a future objective, we review recent progress and challenges in computational techniques that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes.
Department of Computer Science, Hunter College, The City University of New York, New York, New York 10065, USA. lei.xie@hunter.cuny.edu
Lei
L
Xie
Li
L
Xie
Sarah L
SL
Kinnings
Philip E
PE
Bourne
D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D055808:Drug Discovery; D004347:Drug Interactions; D053263:Gene Regulatory Networks; D006801:Humans; D008024:Ligands; D010641:Phenotype; D040901:Proteomics / Q000379:methods
D008024:Ligands