Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype

ChemMedChem. 2022 Jun 20;17(12):e202200161. doi: 10.1002/cmdc.202200161. Epub 2022 May 9.

Abstract

Deep annotation of a library of 4-anilinoquin(az)olines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor (IC50 =14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the cell biology of PKN3 and its role in pancreatic and prostate cancer and T-cell acute lymphoblastic leukemia. These 4-anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases.

Keywords: 4-anilinoquinazoline; 4-anilinoquinoline; Protein Kinase Novel 3 (PKN3); homology model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Male
  • Prostatic Neoplasms*
  • Protein Kinase C
  • Protein Kinase Inhibitors* / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Protein Kinase C