Unmodified methodologies in target discovery for small molecule drugs: A rising star

Target discovery, involving target identification and validation, is the prerequisite for drug discovery and screening. Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease, looking for a drug and elucidating the mechanism of drug treatment. Among the common target identification and confirmation methods, the modified method is time-consuming and laborious, which may reduce or change the activity of natural products. The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets. A wide range of unmodified approaches have been reported, introducing and analyzing the recent emerging methodologies and technologies. This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs. The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research.