Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists

Gillis, Alexander; Gondin, Arisbel B.; Kliewer, Andrea; Sanchez, Julie; Lim, Herman D.; Alamein, Claudia; Manandhar, Pradeep; Santiago, Marina; Fritzwanker, Sebastian; Schmidel, Frank; Katte, Timothy A.; Reekie, Tristan; Grimsey, Natasha L.; Kassiou, Michael; Kellam, Barrie; Krasel, Cornelius; Halls, Michelle L.; Connor, Mark; Lane, J. Robert; Schulz, Stefan; Christie, Macdonald J.; Canals, Meritxell

doi:10.1126/scisignal.aaz3140

All Outputs (5)

Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels (2021)
Journal Article

Fluorescent ligand technologies have proved to be powerful tools to improve our understanding of ligand-receptor interactions. Here we have characterized a small focused library of nine fluorescent ligands based on the highly selective β2-adrenocepto... Read More about Subtype selective fluorescent ligands based on ICI 118,551 to study the human β2‐adrenoceptor in CRISPR/Cas9 genome‐edited HEK293T cells at low expression levels.

Efficient G protein coupling is not required for agonist?mediated internalization and membrane reorganization of the adenosine A 3 receptor (2021)
Journal Article

Organization of G protein-coupled receptors at the plasma membrane has been the focus of much recent attention. Advanced microscopy techniques have shown that these receptors can be localized to discrete microdomains and reorganization upon ligand ac... Read More about Efficient G protein coupling is not required for agonist?mediated internalization and membrane reorganization of the adenosine A 3 receptor.

Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells (2020)
Journal Article

© 2020, The Author(s). To study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the recept... Read More about Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells.

Using Esterase Selectivity to Determine the in Vivo Duration of Systemic Availability and Abolish Systemic Side Effects of Topical ?-Blockers (2020)
Journal Article

© 2020 American Chemical Society. For disorders of the skin, eyes, ears, and respiratory tract, topical drugs, delivered directly to the target organ, are a therapeutic option. Compared with systemic oral therapy, the benefits of topical treatments i... Read More about Using Esterase Selectivity to Determine the in Vivo Duration of Systemic Availability and Abolish Systemic Side Effects of Topical ?-Blockers.

Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists (2020)
Journal Article

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of... Read More about Low intrinsic efficacy for G protein activation can explain the improved side-effect profile of new opioid agonists.