NIR-mbc94, a fluorescent ligand that binds to endogenous CB(2) receptors and is amenable to high-throughput screening

Chem Biol. 2011 May 27;18(5):563-8. doi: 10.1016/j.chembiol.2011.02.016.

Abstract

High-throughput screening (HTS) of chemical libraries is often used for the unbiased identification of compounds interacting with G protein-coupled receptors (GPCRs), the largest family of therapeutic targets. However, current HTS methods require removing GPCRs from their native environment, which modifies their pharmacodynamic properties and biases the screen toward false positive hits. Here, we developed and validated a molecular imaging (MI) agent, NIR-mbc94, which emits near infrared (NIR) light and selectively binds to endogenously expressed cannabinoid CB(2) receptors, a recognized target for treating autoimmune diseases, chronic pain and cancer. The precision and ease of this assay allows for the HTS of compounds interacting with CB(2) receptors expressed in their native environment.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Inverse Agonism
  • Fluorescent Dyes / chemistry*
  • High-Throughput Screening Assays
  • Mice
  • Norbornanes / chemistry
  • Norbornanes / pharmacology*
  • Protein Binding
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB2 / metabolism

Substances

  • Fluorescent Dyes
  • NIR-mbc94
  • Norbornanes
  • Pyrazoles
  • Receptor, Cannabinoid, CB2