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Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932537/ https://www.ncbi.nlm.nih.gov/pubmed/27089349 http://dx.doi.org/10.3390/ph9020019 |
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author | Vasilevich, Natalya I. Tatarskiy, Victor V. Aksenova, Elena A. Kazyulkin, Denis N. Afanasyev, Ilya I. |
author_facet | Vasilevich, Natalya I. Tatarskiy, Victor V. Aksenova, Elena A. Kazyulkin, Denis N. Afanasyev, Ilya I. |
author_sort | Vasilevich, Natalya I. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4932537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-49325372016-07-13 Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model Vasilevich, Natalya I. Tatarskiy, Victor V. Aksenova, Elena A. Kazyulkin, Denis N. Afanasyev, Ilya I. Pharmaceuticals (Basel) Article 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. MDPI 2016-04-13 /pmc/articles/PMC4932537/ /pubmed/27089349 http://dx.doi.org/10.3390/ph9020019 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vasilevich, Natalya I. Tatarskiy, Victor V. Aksenova, Elena A. Kazyulkin, Denis N. Afanasyev, Ilya I. Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title | Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title_full | Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title_fullStr | Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title_full_unstemmed | Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title_short | Search for Potent and Selective Aurora A Inhibitors Based on General Ser/Thr Kinase Pharmacophore Model |
title_sort | search for potent and selective aurora a inhibitors based on general ser/thr kinase pharmacophore model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932537/ https://www.ncbi.nlm.nih.gov/pubmed/27089349 http://dx.doi.org/10.3390/ph9020019 |
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