title: Analysis of drug-induced effect patterns to link structure and side effects of medicines.
abstract: The high failure rate of experimental medicines in clinical trials accentuates inefficiencies of current drug discovery processes caused by a lack of tools for translating the information exchange between protein and organ system networks. Recently, we reported that biological activity spectra (biospectra), derived from in vitro protein binding assays, provide a mechanism for assessing a molecule's capacity to modulate the function of protein-network components. Herein we describe the translation of adverse effect data derived from 1,045 prescription drug labels into effect spectra and show their utility for diagnosing drug-induced effects of medicines. In addition, notwithstanding the limitation imposed by the quality of drug label information, we show that biospectrum analysis, in concert with effect spectrum analysis, provides an alignment between preclinical and clinical drug-induced effects. The identification of this alignment provides a mechanism for forecasting clinical effect profiles of medicines.
authors.affiliation: Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA.
authors.forename: Anton F
authors.initials: AF
authors.lastname: Fliri
authors.forename: William T
authors.initials: WT
authors.lastname: Loging
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thadeio
authors.forename: Robert A
authors.initials: RA
authors.lastname: Volkmann
mesh_terms: D003198:Computer Simulation; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010600:Pharmacology / Q000379:methods*; D011237:Predictive Value of Tests; D020543:Proteome; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations; D020543:Proteome