title: Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model.
abstract: Based on the data for compounds known from the literature to be active against various types of Ser/Thr kinases, a general pharmachophore model for these types of kinases was developed. The search for the molecules fitting to this pharmacophore among the ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against Ser/Thr kinases such as Aurora A, Aurora B and Haspin. Our work on the optimization of these molecules against Aurora A kinase allowed us to achieve several hits in a 3-5 nM range of activity with rather good selectivity and Absorption, Distribution, Metabolism, and Excretion (ADME) properties, and cytotoxicity against 16 cancer cell lines. Thus, we showed the possibility to fine-tune the general Ser/Thr pharmacophore to design active and selective compounds against desired types of kinases.
authors.affiliation: ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. nvasilevich@asinex.com.
authors.forename: Natalya I
authors.initials: NI
authors.lastname: Vasilevich
authors.affiliation: ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. VTatarskiy@asinex.com.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Tatarskiy
authors.affiliation: ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. EAksenova@asinex.com.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Aksenova
authors.affiliation: ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. kazdenis@mail.ru.
authors.forename: Denis N
authors.initials: DN
authors.lastname: Kazyulkin
authors.affiliation: ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. iafanasyev@asinex.com.
authors.forename: Ilya I
authors.initials: II
authors.lastname: Afanasyev
keywords: Aurora A; Ser/Thr kinases; general pharmachophore model