Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease

Chem Commun (Camb). 2017 Dec 19;54(1):42-45. doi: 10.1039/c7cc07581b.

Abstract

The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune cells alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design and synthesize a selective near-infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of metastases in mice reveals predominant probe accumulation in Mer-expressing tumor-associated macrophages.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mice
  • Microscopy, Confocal
  • Molecular Docking Simulation
  • Neoplasm Metastasis
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Structure, Tertiary
  • Pyrimidines / chemistry
  • Pyrroles / chemistry
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Spectroscopy, Near-Infrared*
  • Structure-Activity Relationship
  • c-Mer Tyrosine Kinase / antagonists & inhibitors
  • c-Mer Tyrosine Kinase / genetics
  • c-Mer Tyrosine Kinase / metabolism*

Substances

  • Fluorescent Dyes
  • Pyrimidines
  • Pyrroles
  • Pyrrolo(2,3-d)pyrimidine
  • RNA, Small Interfering
  • c-Mer Tyrosine Kinase