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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Scott, Fiona¹  Fala, Angela M.^2,3  Pennicott, Lewis E.¹  Reuillon, Tristan D.¹  Massirer, Katlin B.^2,3  Elkins, Jonathan M.⁴  Ward, Simon E.^1,5 

[1] Univ Sussex, Sussex Drug Discovery Ctr, Sussex House, Brighton BN1 9RH, E Sussex, England

[2] Univ Estadual Campinas, Ctr Quim Med CQMED, CBMEG, UNICAMP, BR-13083875 Campinas, SP, Brazil

[3] Univ Estadual Campinas, Dept Genet & Evolucao, Inst Biol, Struct Genom Consortium, BR-13083886 Campinas, SP, Brazil

[4] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium, Oxford OX3 7DQ, England

[5] Cardiff Univ, Med Discovery Inst, Main Bldg,Pk Pl, Cardiff CF10 3AT, Wales

关键词: Kinases;    Cancer;    Heart failure;    Inflammation;    AGC kinase;    PKN2;    PRK2;    Protein kinase N2;    Benzimidazole;    Chemical probe;    Chemical tool;   

DOI  :  10.1016/j.bmcl.2020.127040

来源: Elsevier

【 摘 要 】

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

【 授权许可】

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