CINF 7 |
| We present a technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. Starting with 65,000 ligands annotated into sets for hundreds of drug targets, we computed a similarity score between each set using ligand topology. The significance of the resulting similarity scores, normalized using a statistical model, were expressed as a minimum spanning tree to map the sets together. Although these maps are connected solely by chemical similarity, biologically sensible clusters nevertheless emerged. Links among unexpected targets also emerged, among them that methadone, emetine and loperamide (Imodium) may antagonize muscarinic M3, alpha2 adrenergic and neurokinin NK2 receptors, respectively. These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves. It has not escaped our notice that this approach may be useful for drug repurposing. |
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Drug Reprofiling
8:25 AM-12:10 PM, Sunday, August 19, 2007 BCEC -- 252 A, Oral
Division of Chemical Information |