Title:Methods to Profile the Macromolecular Targets of Small Compounds
VOLUME: 16 ISSUE: 30
Author(s):Jianhua Zhu, Wei Wang and Xin Chen
Affiliation:Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, P.R. China, 310058.
Keywords:Drug target, Binding, High-throughput experiment, Virtual screening, Macromolecular.
Abstract: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.
