Tactical Approaches to Interconverting GPCR Agonists and Antagonists

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


There are many reported examples of small structural modifications to GPCR-targeted ligands leading to major changes in their functional activity, converting agonists into antagonists or vice versa. These shifts in functional activity are often accompanied by negligible changes in binding affinity. The current perspective focuses on outlining and analyzing various approaches that have been used to interconvert GPCR agonists, partial agonists, and antagonists in order to achieve the intended functional activity at a GPCR of therapeutic interest. An improved understanding of specific structural modifications that are likely to alter the functional activity of a GPCR ligand may be of use to researchers designing GPCR-targeted drugs and/or probe compounds, specifically in cases where a particular ligand exhibits good potency but not the preferred functional activity at the GPCR of choice.

Original languageEnglish (US)
Pages (from-to)810-840
Number of pages31
JournalJournal of medicinal chemistry
Issue number3
StatePublished - Feb 11 2016

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

Copyright 2018 Elsevier B.V., All rights reserved.


Dive into the research topics of 'Tactical Approaches to Interconverting GPCR Agonists and Antagonists'. Together they form a unique fingerprint.

Cite this