title: Chemogenomics knowledge-based strategies in drug discovery.
abstract: In the postgenomic age of drug discovery, targets can no longer be viewed as singular objects having no relationship to one another. All targets are now visible and the systematic exploration of selected target families appears to be a promising way to speed up and further industrialize target-based drug discovery. Chemogenomics refers to such systematic exploration of target families and aims to identify all possible ligands of all target families. Because biology works by applying prior knowledge to an unknown entity, chemogenomics approaches are expected to be especially effective within the previously well-explored target families, for which, in addition to the protein sequence and structure information, considerable knowledge of pharmacologically active structural classes and structure-activity relationships exists. For the new target families, chemical knowledge will have to be generated and beyond biological target validation, the emphasis is on chemistry to provide the molecules with which their novel biology and pharmacology can be studied. Using examples from the previously most successfully explored target families, the GPCR family in particular, we summarize herein our current chemogenomics knowledge-based strategies for drug discovery, which are founded on the high integration of chem and bioinformatics, thereby providing a molecular informatics frame for the exploration of the new target families.
authors.affiliation: Compound Management and Computation Unit, Novartis Lead Discovery Center, Novartis Pharma AG, Basel, Switzerland. edgar.jacoby@pharma.novartis.com
authors.forename: Edgar
authors.initials: E
authors.lastname: Jacoby
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schuffenhauer
authors.forename: Philipp
authors.initials: P
authors.lastname: Floersheim
mesh_terms: D019295:Computational Biology / Q000639:trends; D016208:Databases, Factual / Q000639:trends; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000378:metabolism; D023281:Genomics / Q000639:trends*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels; D008024:Ligands; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D019204:GTP-Binding Proteins