title: A chemical genetic approach for covalent inhibition of analogue-sensitive aurora kinase.
abstract: The perturbation of protein kinases with small organic molecules is a powerful approach to dissect kinase function in complex biological systems. Covalent kinase inhibitors that target thiols in the ATP binding pocket of the kinase domain proved to be ideal reagents for the investigation of highly dynamic cellular processes. However, due to the covalent inhibitors' possible off-target reactivities, it is required that the overall shape of the inhibitor as well as the intrinsic reactivity of the electrophile are precisely tuned to favor the reaction with only the desired cysteine. Here we report on the design and biological characterization of covalent anilinoquinazolines as potent inhibitors of genetically engineered Aurora kinase in fission yeast.
authors.affiliation: Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Koch
authors.forename: Haridas B
authors.initials: HB
authors.lastname: Rode
authors.forename: André
authors.initials: A
authors.lastname: Richters
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
authors.forename: Silke
authors.initials: S
authors.lastname: Hauf
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D064127:Aurora Kinases; D015195:Drug Design; D005818:Genetic Engineering; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology*; D012568:Schizosaccharomyces
chemical_list: D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C023650:aniline