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PMID: 28753422 Published · ppublish English Journal Article Review

How Ligands Illuminate GPCR Molecular Pharmacology.

Cell ·Vol. 170 ·No. 3 ·2017-07-27 ·Pages 414-427

Wacker D, Stevens RC, Roth BL

Abstract

G protein-coupled receptors (GPCRs), which are modulated by a variety of endogenous and synthetic ligands, represent the largest family of druggable targets in the human genome. Recent structural and molecular studies have both transformed and expanded classical concepts of receptor pharmacology and have begun to illuminate the distinct mechanisms by which structurally, chemically, and functionally diverse ligands modulate GPCR function. These molecular insights into ligand engagement and action have enabled new computational methods and accelerated the discovery of novel ligands and tool compounds, especially for understudied and orphan GPCRs. These advances promise to streamline the development of GPCR-targeted medications.

MeSH Terms
Animals Drug Discovery Humans Ligands Models, Molecular Molecular Targeted Therapy Receptors, G-Protein-Coupled/antagonists & inhibitors,chemistry,metabolism Signal Transduction
Chemicals
Ligands Receptors, G-Protein-Coupled
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wacker Daniel
Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27514, USA.
Stevens Raymond C
Departments of Biological Sciences and Chemistry, Bridge Institute, University of Southern California, Los Angeles, CA 90089, USA.
Roth Bryan L
Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27514, USA. Electronic address: bryan_roth@med.unc.edu.
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2017.07.009
Email
bryan_roth@med.unc.edu
Published
2017-07-27
Pages
414-427
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC5560499
Subset
IM
Grants
NIMH NIH HHS · U19 MH082441 · United States
NIMH NIH HHS · R01 MH112205 · United States
NIDA NIH HHS · P01 DA035764 · United States
NIDDK NIH HHS · U24 DK116195 · United States
NIMH NIH HHS · U01 MH104974 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2017.07.009 PMC Full Text View journal details
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