The role of kinetic context in apparent biased agonism at GPCRs

Javitch, Jonathan A.; Klein Herenbrink, Carmen; Sykes, David A.; Donthamsetti, Prashant; Canals, Meritxell; Coudrat, Thomas; Shonberg, Jeremy; Scammells, Peter J.; Capuano, Ben; Sexton, Patrick M.; Charlton, Steven J.; Javitch, Jonathan; Christopoulos, Arthur; Lane, J. Robert

doi:10.1038/ncomms10842

All Outputs (4)

Uncoupling the Structure–Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding (2016)
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Ligand binding to membrane proteins may be significantly influenced by the interaction of ligands with the membrane. In particular, the microscopic ligand concentration within the membrane surface solvation layer may exceed that in bulk solvent, resu... Read More about Uncoupling the Structure–Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding.

Fevipiprant (QAW039), a slowly dissociating CRTh2 antagonist with the potential for improved clinical efficacy (2016)
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Here we describe the pharmacologic properties of a series of clinically relevant chemoattractant receptor-homologous molecules expressed on T-helper type 2 (CRTh2) receptor antagonists, including fevipiprant (NVP-QAW039 or QAW039), which is currently... Read More about Fevipiprant (QAW039), a slowly dissociating CRTh2 antagonist with the potential for improved clinical efficacy.

Long receptor residence time of C26 contributes to super agonist activity at the human ?2 adrenoceptor (2016)
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Super agonists produce greater functional responses than endogenous agonists in the same assay, and their unique pharmacology is the subject of increasing interest and debate. We propose that receptor residence time and the duration of receptor signa... Read More about Long receptor residence time of C26 contributes to super agonist activity at the human ?2 adrenoceptor.

The role of kinetic context in apparent biased agonism at GPCRs (2016)
Journal Article

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usu... Read More about The role of kinetic context in apparent biased agonism at GPCRs.