Pharmacobiology Section

Abstract Heterotrimeric G protein subunits Gαq and Gα11 are inhibited by two cyclic depsipeptides, FR900359 (FR) and YM-254890 (YM), both of which are being used widely to implicate Gq/11 proteins in the regulation of diverse biological processes. An emerging major research question therefore is whether the cellular effects of both inhibitors are on-target, i.e. mediated via specific inhibition of Gq/11 proteins, or off-target, i.e. the result of nonspecific interactions with other proteins.

Bachelerie F. Ben-Baruch A. Burkhardt A.M. Combadiere C. Farber J.M. Graham G.J. Horuk R. Sparre-Ulrich A.H. Locati M. Luster A.D. et al. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol. Rev. 2013; 66: 1-79 Bae Y.-S. Lee T.G. Park J.C. Hur J.H. Kim Y. Heo K. Kwak J.-Y. Suh P.-G.

The Nociceptin/Orphanin FQ (N/OFQ) peptide NOP receptor is coupled to pertussis toxin (PTX)-sensitive G proteins (G i/o ) whose activation leads to the inhibition of both cAMP production and calcium channel activity, and to the stimulation of potassium currents. The label free dynamic mass redistribution (DMR) approach has been demonstrated useful for investigating the pharmacological profile of G protein-coupled receptors.