Recent Progress in Assays for GPCR Drug Discovery.

G-protein coupled receptors (GPCRs), also known as 7 transmembrane receptors, are the largest family of cell surface receptors in eukaryotes. There are ~800 GPCRs in human, regulating diverse physiological processes. GPCRs are the most intensively studied drug targets. Drugs that target GPCRs account for about a quarter of the global market share of therapeutic drugs. Therefore, to develop physiologically relevant and robust assays to search new GPCR ligands or modulators remain the major focus of drug discovery research worldwide. Early functional GPCR assays are mainly depend on the measurement of G protein-mediated second messenger generation. Recent development in GPCR biology indicate the signaling of these receptors is much more complex than the oversimplified classical view. GPCRs have been found to activate multiple G proteins simultaneously and induce b-arrestin-mediated signaling. GPCRs have also been found to interacte with other cytosolic scaffolding proteins and form dimer or heteromer with GPCRs or other transmembrane proteins. Here we mainly discuss technologies focused on detecting protein-protein interactions, such as FRET/BRET, NanoBiT, Tango, etc, and their applications in measuring GPCRs interacting with various signaling partners. In the final part, we also discuss the species differences in GPCRs when using animal models to study the in vivofunctions of GPCR ligands, and possible ways to solve this problem with modern genetic tools.

• Publication year

  2022

• Venue

  American Journal of Physiology - Cell Physiology

• Publication date

  2022-07-11

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1152/ajpcell.00464.2021PMID 35816640
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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