title: Assay Related Target Similarity (ARTS) - chemogenomics approach for quantitative comparison of biological targets.
abstract: Computer-based chemogenomics approaches compare macromolecular drug targets based on their amino acid sequences or derived properties, by similarity of their ligands, or according to ligand-target interaction models. Here we present ARTS (Assay Related Target Similarity) as a quantitative index that estimates target similarity directly from measured affinities of a set of probe compounds. This approach reduces the risk of deducing artificial target relationships from mutually inactive compounds. ARTS implements a scoring scheme that matches intertarget similarity based on dose-response measurements. While all experimentally derived target similarities have a tendency to be data set-dependent, we demonstrate that ARTS depends less on the used data set than the commonly used Pearson correlation or Tanimoto index.
authors.affiliation: Lead Identification and Optimization Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. michael.bieler@boehringer-ingelheim.com
authors.forename: Michael
authors.initials: M
authors.lastname: Bieler
authors.forename: Ralf
authors.initials: R
authors.lastname: Heilker
authors.forename: Herbert
authors.initials: H
authors.lastname: Köppen
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled