Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer

Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (<20%) have been investigated for their therapeutic viability, likely due to the lack of available chemical...

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Autores principales: Scott, Fiona, Fala, Angela M., Pennicott, Lewis E., Reuillon, Tristan D., Massirer, Katlin B., Elkins, Jonathan M., Ward, Simon E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078758/
https://www.ncbi.nlm.nih.gov/pubmed/32085971
http://dx.doi.org/10.1016/j.bmcl.2020.127040
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author Scott, Fiona
Fala, Angela M.
Pennicott, Lewis E.
Reuillon, Tristan D.
Massirer, Katlin B.
Elkins, Jonathan M.
Ward, Simon E.
author_facet Scott, Fiona
Fala, Angela M.
Pennicott, Lewis E.
Reuillon, Tristan D.
Massirer, Katlin B.
Elkins, Jonathan M.
Ward, Simon E.
author_sort Scott, Fiona
collection PubMed
description Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (<20%) have been investigated for their therapeutic viability, likely due to the lack of available chemical tools across the kinome. In this work we describe initial efforts in the development of a selective chemical tool for protein kinase N2 (PKN2), a relatively unexplored kinase of interest in several types of cancer. The most successful compound, 5, has a measured IC(50) of 0.064 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1.
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spelling pubmed-70787582020-04-15 Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer Scott, Fiona Fala, Angela M. Pennicott, Lewis E. Reuillon, Tristan D. Massirer, Katlin B. Elkins, Jonathan M. Ward, Simon E. Bioorg Med Chem Lett Article Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (<20%) have been investigated for their therapeutic viability, likely due to the lack of available chemical tools across the kinome. In this work we describe initial efforts in the development of a selective chemical tool for protein kinase N2 (PKN2), a relatively unexplored kinase of interest in several types of cancer. The most successful compound, 5, has a measured IC(50) of 0.064 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1. Elsevier Science Ltd 2020-04-15 /pmc/articles/PMC7078758/ /pubmed/32085971 http://dx.doi.org/10.1016/j.bmcl.2020.127040 Text en © 2020 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scott, Fiona
Fala, Angela M.
Pennicott, Lewis E.
Reuillon, Tristan D.
Massirer, Katlin B.
Elkins, Jonathan M.
Ward, Simon E.
Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title_full Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title_fullStr Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title_full_unstemmed Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title_short Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer
title_sort development of 2-(4-pyridyl)-benzimidazoles as pkn2 chemical tools to probe cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078758/
https://www.ncbi.nlm.nih.gov/pubmed/32085971
http://dx.doi.org/10.1016/j.bmcl.2020.127040
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