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.
Bioorg Med Chem Lett
AGC kinase, Benzimidazole, Cancer, Chemical probe, Chemical tool, Heart failure, Inflammation, Kinases, PKN2, PRK2, Protein kinase N2, Antineoplastic Agents, Benzimidazoles, Crystallography, X-Ray, Dose-Response Relationship, Drug, Drug Development, Humans, Models, Molecular, Molecular Structure, Neoplasms, Protein Kinase C, Protein Kinase Inhibitors, Structure-Activity Relationship