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Vasilevich NI, Tatarskiy VV, Aksenova EA, et al. Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model. Pharmaceuticals (Basel). 2016;9(2)doi: 10.3390/ph9020019.
Vasilevich, N. I., Tatarskiy, V. V., Aksenova, E. A., Kazyulkin, D. N., & Afanasyev, I. I. (2016). Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model. Pharmaceuticals (Basel, Switzerland), 9(2), . https://doi.org/10.3390/ph9020019
Vasilevich, Natalya I, et al. "Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model." Pharmaceuticals (Basel, Switzerland) vol. 9,2 (2016). doi: https://doi.org/10.3390/ph9020019
Vasilevich NI, Tatarskiy VV, Aksenova EA, Kazyulkin DN, Afanasyev II. Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model. Pharmaceuticals (Basel). 2016 Apr 13;9(2). doi: 10.3390/ph9020019. PMID: 27089349; PMCID: PMC4932537.
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Pharmaceuticals (Basel). 2016 Apr 13;9(2). doi: 10.3390/ph9020019.

Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model.

Pharmaceuticals (Basel, Switzerland)

Natalya I Vasilevich, Victor V Tatarskiy, Elena A Aksenova, Denis N Kazyulkin, Ilya I Afanasyev

Affiliations

  1. ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. [email protected].
  2. ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. [email protected].
  3. ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. [email protected].
  4. ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. [email protected].
  5. ASINEX Company Group, Novie Nauchnie Tekhnologii Ltd., 20 Geroev Panfilovtsev Street, Moscow 125480, Russia. [email protected].

PMID: 27089349 PMCID: PMC4932537 DOI: 10.3390/ph9020019

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.

Keywords: Aurora A; Ser/Thr kinases; general pharmachophore model

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