title: General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors.
abstract: A general pharmachophore model for various types of Ser/Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3-5 nm range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained.
authors.affiliation: Novie Nauchnie Tekhnologii Ltd. (ASINEX Company Group), 20 Geroev Panfilovtsev Str., Moscow, 125480, Russia.
authors.forename: Natalya I
authors.initials: NI
authors.lastname: Vasilevich
authors.affiliation: Novie Nauchnie Tekhnologii Ltd. (ASINEX Company Group), 20 Geroev Panfilovtsev Str., Moscow, 125480, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Aksenova
authors.affiliation: Novie Nauchnie Tekhnologii Ltd. (ASINEX Company Group), 20 Geroev Panfilovtsev Str., Moscow, 125480, Russia.
authors.forename: Denis N
authors.initials: DN
authors.lastname: Kazyulkin
authors.affiliation: Novie Nauchnie Tekhnologii Ltd. (ASINEX Company Group), 20 Geroev Panfilovtsev Str., Moscow, 125480, Russia.
authors.forename: Ilya I
authors.initials: II
authors.lastname: Afanasyev
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: kinase; molecular modeling; pharmacophore modeling; phosphatase; structure-based drug design