Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model
by
Natalya I. Vasilevich *, Victor V. Tatarskiy, Elena A. Aksenova, Denis N. Kazyulkin and Ilya I. Afanasyev
Natalya I. Vasilevich *, Victor V. Tatarskiy, Elena A. Aksenova, Denis N. Kazyulkin and Ilya I. Afanasyev
ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Pharmaceuticals 2016, 9(2), 19; https://doi.org/10.3390/ph9020019
Received: 21 December 2015 / Revised: 29 March 2016 / Accepted: 1 April 2016 / Published: 13 April 2016
(This article belongs to the Special Issue Selected Papers from the 1st International Electronic Conference on Medicinal Chemistry)
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.
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Keywords:
general pharmachophore model; Ser/Thr kinases; Aurora A
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MDPI and ACS Style
Vasilevich, N.I.; Tatarskiy, V.V.; Aksenova, E.A.; Kazyulkin, D.N.; Afanasyev, I.I. Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model. Pharmaceuticals 2016, 9, 19.
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