Systems Pharmacology

The “one-target, one-drug, one-disease” model has long been the standard strategy for discovering new drugs in pharmaceutical research. In spite of the fact that this paradigm allowed discovering new drugs, a meaningful decrease in the rate of new drug candidates has been observed. In the last decade, many failures in drug development have occurred in the clinical trial stage, and the number of new drugs approved by the US Food and Drug Administration’s (FDA) has decreased. The main reason for this is that, whereas the multiple activities of drugs against several targets might be beneficial, it can also lead to dramatic side effects and toxicity. Nowadays increasing evidence that several drugs exert their biological effects through interactions with multiple targets is boosting the development of new research such as systems polypharmacology and chemogenomics [1]. Therefore the purpose of drug discovery has changed from one-drug, one-target strategy to a multi-drug, multi-target approach by systems pharmacology [2]. Systems pharmacology is the application of network biology principles to the field of drug discovery. Systems pharmacology seeks to understand how drugs affect the human body as a complex biological system (on specific pathways, on different cell types and in different tissues/organs/diseases). The complex biological system may include drug-protein, protein-protein, genetic, signaling and physiological (at cellular, tissue, organ and whole body levels). It uses bioinformatics and statistical techniques to integrate and interpret these networks. In this lecture, I will describe the current state of multi-target drug discovery and the concepts of systems pharmacology, drug repurposing, polypharmacology, chemogenomics, and phenotypic screening.