Allosteric inhibition of g-protein coupled receptor oligomerization: Strategies and challenges for drug development

Mattan Hurevich, Alaa Talhami, Deborah E. Shalev, Chaim Gilon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


G-protein coupled receptors (GPCRs) mediate a large number of biological pathways and are major therapeutic targets. One of the most exiting phenomena of GPCRs is their ability to interact with other GPCRs. GPCRGPCR interactions, also known as GPCR oligomerization, may create various functional entities such as homo- and heterodimers and also form complex multimeric GPCR clusters. In many biological systems, GPCR-GPCR interactions are crucial for signal regulation. The interaction with other receptors results in allosteric modifications of GPCRs through conformational changes. Allosteric inhibition of GPCRs is considered an attractive strategy for drug development and does not involve targeting the orthosteric site. Understanding the nature of GPCR-GPCR interactions is mandatory for developing allosteric inhibitors. Studying GPCR-GPCR interactions is a challenging task and many methods have been developed to analyze these events. This review will highlight some of the methods developed to study GPCR-GPCR interactions and will describe pivotal studies that provided the basic understanding of the importance of GPCR oligomerization. We will also describe the significance of GPCR interaction networks for drug development. Recent studies will be reviewed to illustrate the use of state-of-the-art biophysical and spectroscopic methods for the discovery of GPCR oligomerization modulators.

Original languageAmerican English
Pages (from-to)1842-1863
Number of pages22
JournalCurrent Topics in Medicinal Chemistry
Issue number15
StatePublished - 1 Jan 2014

Bibliographical note

Publisher Copyright:
© 2014 Bentham Science Publishers


  • Allosteric inhibition
  • Chemokine receptors
  • GPCR inhibition
  • GPCR oligomerization
  • GPCR-GPCR interactions
  • Gprotein coupled receptors
  • Helix mimetic


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