title: Drug effect prediction by polypharmacology-based interaction profiling.
abstract: Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able to relate complex drug-protein interaction profiles with effect profiles. Structural data and registered effect profiles of all small-molecule drugs were collected, and interactions to a series of nontarget protein binding sites of each drug were calculated. Statistical analyses confirmed a close relationship between the studied 177 major effect categories and interaction profiles of ca. 1200 FDA-approved small-molecule drugs. On the basis of this relationship, the effect profiles of drugs were revealed in their entirety, and hitherto uncovered effects could be predicted in a systematic manner. Our results show that the prediction power is independent of the composition of the protein set used for interaction profile generation.
authors.affiliation: Department of Biochemistry, Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/C, H-1117 Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Simon
authors.forename: Agnes
authors.initials: A
authors.lastname: Peragovics
authors.forename: Margit
authors.initials: M
authors.lastname: Vigh-Smeller
authors.forename: Gábor
authors.initials: G
authors.lastname: Csukly
authors.forename: László
authors.initials: L
authors.lastname: Tombor
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Yang
authors.forename: Gergely
authors.initials: G
authors.lastname: Zahoránszky-Kohalmi
authors.forename: László
authors.initials: L
authors.lastname: Végner
authors.forename: Balázs
authors.initials: B
authors.lastname: Jelinek
authors.forename: Péter
authors.initials: P
authors.lastname: Hári
authors.forename: Csaba
authors.initials: C
authors.lastname: Hetényi
authors.forename: István
authors.initials: I
authors.lastname: Bitter
authors.forename: Pál
authors.initials: P
authors.lastname: Czobor
authors.forename: András
authors.initials: A
authors.lastname: Málnási-Csizmadia
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D054316:Biomarkers, Pharmacological / Q000032:analysis*; D016208:Databases, Factual; D006801:Humans; D055553:Prescription Drugs / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011506:Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012372:ROC Curve; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054316:Biomarkers, Pharmacological; D055553:Prescription Drugs; D011506:Proteins; D054852:Small Molecule Libraries