Dogma shift in receptor pharmacology – deeper understanding of Frizzleds as pharmacological targets

G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors in humans. They are currently the target of more than a third of all pharmaceuticals on the market and of large importance in the future development and improvement of treatments for human disease.

Intrinsic to development, cellular health and disease, Frizzleds (FZDs) – the cell surface receptors that the Schulte laboratory focuses on – belong to a subfamily of GPCRs that has been subject to controversy over the last few decades due to a lack of tools available to assess their ability to function like typical GPCRs.

In their review published in Trends in Pharmacological Sciences, Gunnar Schulte and Shane Wright, from the Department of Pharmacology at Karolinska Institutet, provide an update on the status of FZDs as GPCRs and discuss recent findings from the Schulte Lab and others that unequivocally demonstrate the GPCR “nature” of these receptors. Application of well-established methodology and concepts pertinent to classical GPCRs - such as the receptors for adrenalin, histamine, dopamine or serotonin - will continue to be helpful in understanding the function and assessing the druggability of FZDs.

From a pharmacological and structural standpoint, understanding how these molecular machines operate will guide future drug discovery efforts and it is the hope of the authors that their exhaustive exposé of the literature will become the basis for more experiments that will aid in this endeavor.