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

ABSTRACT: 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 IC50 of 0.064 ?M against PKN2, with ca. 17-fold selectivity over close homologue, PKN1.

SUBMITTER: Scott F

PROVIDER: S-EPMC7078758 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Scott Fiona F Fala Angela M AM Pennicott Lewis E LE Reuillon Tristan D TD Massirer Katlin B KB Elkins Jonathan M JM Ward Simon E SE

Bioorganic & medicinal chemistry letters 20200217 8

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 ...[more]

PMID: 32085971

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