Jianhua Zhu, Wei Wang and Xin Chen Pages 3657 - 3667 ( 11 )
Small compounds constitute most of the available medicines. However, their stereophysical and stereochemical properties are relatively simple, which typically results in promiscuity in their interactions with human proteins. Such promiscuity has caused problems in our past efforts to discover and develop new drugs, but at the same time, it also brought us new opportunities to exploit the off-target interactions between small compounds and human proteins for novel or improved therapeutics, e.g. in applications of polypharmacology, drug repositioning, and rational design of drug combinations. In this direction, identifying the full profile of macromolecules that a small compound may interact with is of fundamental importance to harnessing the positive side of small compound promiscuity. This review summarizes available experimental and computational approaches that identify macromolecular targets for small compounds. The principle, application, performance, limitation and availability of these approaches are discussed.
Drug target, Binding, High-throughput experiment, Virtual screening, Macromolecular.
Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, P.R. China, 310058.