Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery.

Journal Article (Journal Article;Review)

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in the genome and the most successful family of targets of FDA-approved drugs. New frontiers in GPCR drug discovery remain, however, as achieving receptor subtype selectivity and controlling off- and on-target side effects are not always possible with classic agonist and antagonist ligands. These challenges may be overcome by focusing development efforts on allosteric ligands that confer signaling bias. Biased allosteric modulators (BAMs) are an emerging class of GPCR ligands that engage less well-conserved regulatory motifs outside the orthosteric pocket and exert pathway-specific effects on receptor signaling. The unique ways that BAMs texturize receptor signaling present opportunities to fine-tune physiology and develop safer, more selective therapeutics. Here, we provide a conceptual framework for understanding the pharmacology of BAMs, explore their therapeutic potential, and discuss strategies for their discovery.

Full Text

Duke Authors

Cited Authors

  • Slosky, LM; Caron, MG; Barak, LS

Published Date

  • April 2021

Published In

Volume / Issue

  • 42 / 4

Start / End Page

  • 283 - 299

PubMed ID

  • 33581873

Electronic International Standard Serial Number (EISSN)

  • 1873-3735

Digital Object Identifier (DOI)

  • 10.1016/


  • eng

Conference Location

  • England