Faculty Opinions recommendation of Drug-target network.
Arthur Christopoulos · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2007
The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed. PMID: 17921997 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: U56 CA113004 PHS HHS, United States Grant ID: U01 A1070499-01 NHGRI NIH HHS, United States Grant ID: 2R01 HG001715