Drugs in other drugs: a new look at drugs as fragments.
The authors of this review have examined the complete set of marketed drugs, with regards to looking for structural similarities between drugs. By comparing the structures of all drugs, it has been established how many times one marketed drug occurred as a substructure within another marketed drug. A total of 209 from 1386 marketed drugs sized between 100 and 1500 Da (i.e. 15% of the 1386 total) are contained within other drugs, differing by one or more continuous chemical fragment, and as many as 418 drugs from the total of 1386 (i.e. 30%) contain other drugs as substructure fragments. Many smaller drugs occur in multiple larger drugs. Most of the small changes tend to retain primary indicated pharmacology, whereas larger changes more often lead to different primary pharmacology. We identify a subset of drugs that can be used in fragment-based drug discovery strategies. In addition, the analysis enhances understanding of marketed drug space from the chemical building-block perspective.
Siegel
Miles G
MG
Discovery Chemistry Research, Lilly Research Laboratories, Lilly Corporate Center, IN 46285, USA.
Vieth
Michal
M
D015195:Drug Design; D015394:Molecular Structure; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000145:classification; D021281:Quantitative Structure-Activity Relationship
D004364:Pharmaceutical Preparations