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 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1.