2-Aminophenylpyrimidines as Novel Inhibitors of Aminoacyl-tRNA Synthetase Interacting Multifunctional Protein 2 (AIMP2)-DX2 for Lung Cancer Treatment

J Med Chem. 2020 Apr 23;63(8):3908-3914. doi: 10.1021/acs.jmedchem.9b01765. Epub 2020 Apr 1.

Abstract

Aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMPs) have recently been considered novel therapeutic targets in several cancers. In this publication we report the development of novel 2-aminophenylpyrimidines as new AIMP2-DX2 inhibitors. In particular, aminophenylpyrimidine 3 not only exhibited promising in vitro and in vivo potency but also exerted selective inhibition of H460 and A549 cells and AIMP2-DX2 rather than WI-26 cells and AIMP2. Aminophenylpyrimidine 3 offers possible therapeutic potential in the treatment of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Amino Acyl-tRNA Synthetases / antagonists & inhibitors*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods

Substances

  • AIMP2 protein, human
  • Nuclear Proteins
  • Pyrimidines
  • Amino Acyl-tRNA Synthetases