Regulation of µ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance

JT Williams, SL Ingram, G Henderson, C Chavkin… - Pharmacological …, 2013 - Elsevier
Morphine and related µ-opioid receptor (MOR) agonists remain among the most effective
drugs known for acute relief of severe pain. A major problem in treating painful conditions is …

[BOOK][B] Bioassay techniques for drug development

MI Choudhary, WJ Thomsen - 2001 - taylorfrancis.com
The goal of an activity-directed isolation process is to isolate bioactive compounds which
may provide structural leads of therapeutic importance. Whereas the traditional process of …

[HTML][HTML] A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model.

P Samama, S Cotecchia, T Costa… - Journal of Biological …, 1993 - Elsevier
We have replaced the C-terminal portion of the third intracellular loop of the beta 2-
adrenergic receptor (residues 266-272) with the homologous region of the alpha 1B …

Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex

YL Liang, M Khoshouei, A Glukhova, SGB Furness… - Nature, 2018 - nature.com
The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major target for
the treatment of type 2 diabetes and obesity. Endogenous and mimetic GLP-1 peptides …

Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation

DP Staus, RT Strachan, A Manglik, B Pani, AW Kahsai… - Nature, 2016 - nature.com
G-protein-coupled receptors (GPCRs) modulate many physiological processes by
transducing a variety of extracellular cues into intracellular responses. Ligand binding to an …

Allosteric binding sites on cell-surface receptors: novel targets for drug discovery

A Christopoulos - Nature reviews Drug discovery, 2002 - nature.com
Cell-surface receptors are the targets for more than 60% of current drugs. Traditionally,
optimizing the interaction of lead molecules with the binding site for the endogenous agonist …

Allosteric modulation of G protein–coupled receptors

LT May, K Leach, PM Sexton… - Annu. Rev. Pharmacol …, 2007 - annualreviews.org
The past decade has witnessed a significant growth in the identification of allosteric
modulators of G protein–coupled receptors (GPCRs), ie, ligands that interact with binding …

Affinity, potency and efficacy of tramadol and its metabolites at the cloned human µ-opioid receptor

C Gillen, M Haurand, DJ Kobelt, S Wnendt - … -Schmiedeberg's archives of …, 2000 - Springer
The present study was conducted to characterise the centrally active analgesic drug
tramadol hydrochloride [(1 RS, 2 RS)-2-[(dimethyl-amino)-methyl]-1-(3-methoxyphenyl) …

Allosteric modulation of G protein-coupled receptors: a pharmacological perspective

P Keov, PM Sexton, A Christopoulos - Neuropharmacology, 2011 - Elsevier
G protein-coupled receptor (GPCR)-based drug discovery has traditionally focused on
targeting the orthosteric site for the endogenous agonist. However, many GPCRs possess …

Graded activation and free energy landscapes of a muscarinic G-protein–coupled receptor

Y Miao, JA McCammon - Proceedings of the National …, 2016 - National Acad Sciences
G-protein–coupled receptors (GPCRs) recognize ligands of widely different efficacies, from
inverse to partial and full agonists, which transduce cellular signals at differentiated levels …