Cell- and Tissue-Based Proteome Profiling and Bioimaging with Probes Derived from a Potent AXL Kinase Inhibitor

Chem Asian J. 2018 Sep 17;13(18):2601-2605. doi: 10.1002/asia.201800605. Epub 2018 Aug 7.

Abstract

AXL has been defined as a novel target for cancer therapeutics. However, only a few potent and selective inhibitors targeting AXL are available to date. Recently, our group has developed a lead compound, 9im, capable of displaying potent and specific inhibition of AXL. To further identify the cellular on/off targets, in this study, competitive affinity-based proteome profiling was carried out, leading to the discovery of several unknown cellular targets such as BCAP31, LPCAT3, POR, TM9SF3, SCCPDH and CANX. In addition, trans-cyclooctene (TCO) and acedan-containing probes were developed to image the binding between 9im and its target proteins inside live cells and tumor tissues. These probes would be useful tools in the detection of AXL in various biosystems.

Keywords: AXL; imaging; probes; proteomics; target identification.

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase
  • Cell Line, Tumor
  • Click Chemistry
  • Fluorescence
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Fluorescent Dyes / radiation effects
  • Humans
  • Male
  • Mice, Inbred ICR
  • Microscopy, Fluorescence
  • Molecular Docking Simulation
  • Photoaffinity Labels / chemistry
  • Photoaffinity Labels / metabolism*
  • Photoaffinity Labels / radiation effects
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / radiation effects
  • Proteome / chemistry
  • Proteome / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / chemistry
  • Quinolones / chemistry
  • Quinolones / metabolism*
  • Quinolones / pharmacology
  • Quinolones / radiation effects
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Ultraviolet Rays

Substances

  • Fluorescent Dyes
  • Photoaffinity Labels
  • Protein Kinase Inhibitors
  • Proteome
  • Proto-Oncogene Proteins
  • Quinolones
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase