title: Pseudokinase drug intervention: a potentially poisoned chalice.
abstract: Pseudokinases, the catalytically impaired component of the kinome, have recently been found to share more properties with active kinases than previously thought. In many pseudokinases, ATP binding and even some activity is preserved, highlighting these proteins as potential drug targets. In both active kinases and pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can stabilize specific conformations required for activity and protein-protein interactions. We discuss the implications of locking particular conformations in a selection of (pseudo)kinases and the dual potential impact on the druggability of these proteins.
authors.affiliation: Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK. jeroen.claus@cancer.org.uk
authors.forename: Jeroen
authors.initials: J
authors.lastname: Claus
authors.forename: Angus J M
authors.initials: AJ
authors.lastname: Cameron
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D055162:Biocatalysis; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases