title: Mapping of inhibitors and activity data to the human kinome and exploring promiscuity from a ligand and target perspective.
abstract: An up-to-date collection of publicly available kinase inhibitors and activity data was mapped to the human kinome to comprehensively analyze current small molecule-kinase interactions. Compound distributions across the kinome were explored, structural relationships between inhibitors determined, and the tendency to form activity cliffs assessed. Furthermore, promiscuity was analyzed at the level of inhibitors and kinases, and a number of kinase targets with distinct preferences for single- or multitarget inhibitors were identified. Taken together, the results of current analysis provide a detailed view of kinase-inhibitor interaction characteristics across the human kinome.
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kunimoto
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
mesh_terms: D018390:Gene Targeting; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D010770:Phosphotransferases / Q000737:chemistry / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D010770:Phosphotransferases
keywords: activity cliffs; activity data; human kinome; inhibitors; ligand and target promiscuity; matched molecular pairs; protein kinases