Lead compound optimization strategy (2)--structure optimization strategy for reducing toxicity risks in drug design.
- Author:
Hai-Long LIU
;
Jiang WANG
;
Dai-Zong LIN
;
Hong LIU
- Publication Type:Journal Article
- MeSH:
Binding Sites;
Cytochrome P-450 Enzyme System;
metabolism;
Drug Design;
Drug Discovery;
methods;
Drug Recalls;
Drug-Related Side Effects and Adverse Reactions;
prevention & control;
Humans;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2014;49(1):1-15
- CountryChina
- Language:Chinese
-
Abstract:
Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
