[Lead compound optimization strategy (2)--structure optimization strategy for reducing toxicity risks in drug design].
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.
Hai-Long
HL
Liu
Jiang
J
Wang
Dai-Zong
DZ
Lin
Hong
H
Liu
D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D056736:Drug Recalls; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D006801:Humans; D013329:Structure-Activity Relationship
D003577:Cytochrome P-450 Enzyme System