Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

International Journal of Molecular Sciences

卷:21

CongBao Kang¹  Qingxin Li² 

[1] Experimental Drug Development Centre (EDDC), Agency for Science, Technology and Research (A*STAR), 10 Biopolis Road, Chromos, 05-01, Singapore 138670, Singapore;

[2] Guangdong Provincial Engineering Laboratory of Biomass High Value Utilization, Guangdong Provincial Bioengineering Institute (Guangzhou Sugarcane Industry Research Institute), Guangdong Academy of Sciences, Guangzhou 510316, China;

关键词: small-molecule drugs;    drug discovery;    structural biology;    mechanism of action;    inhibitors;    chemical biology;   

DOI  :  10.3390/ijms21155262

来源: DOAJ

【 摘 要 】

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

【 授权许可】

Unknown