Functional selectivity of Receptor Tyrosine Kinases regulates distinct cellular outputs [PDF]
Frontiers in Cell and Developmental Biology, 2023 Functional selectivity refers to the activation of differential signalling and cellular outputs downstream of the same membrane-bound receptor when activated by two or more different ligands.
Sakim S. Samad +4 more
doaj +4 more sources
Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site [PDF]
eLife, 2021 Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood.
Rajendra Uprety +23 more
doaj +2 more sources
Functional Selectivity Does Not Predict Antinociceptive/Locomotor Impairing Potencies of NOP Receptor Agonists [PDF]
Frontiers in Neuroscience, 2021 Nociceptin/orphanin FQ controls several functions, including pain transmission, via stimulation of the N/OFQ peptide (NOP) receptor. Here we tested the hypothesis that NOP biased agonism may be instrumental for identifying innovative analgesics. In vitro
Joaquim Azevedo Neto +7 more
doaj +2 more sources
Functional selectivity of EM-2 analogs at the mu-opioid receptor [PDF]
Frontiers in Pharmacology, 2023 The mu opioid receptor agonists are the most efficacious pain controlling agents but their use is accompanied by severe side effects. More recent developments indicate that some ligands can differentially activate receptor downstream pathways, possibly ...
Justyna Piekielna-Ciesielska +6 more
doaj +2 more sources
Functional Selectivity and Antinociceptive Effects of a Novel KOPr Agonist [PDF]
Frontiers in Pharmacology, 2020 Kappa opioid receptor (KOPr) agonists represent alternative analgesics for their low abuse potential, although relevant adverse effects have limited their clinical use.
Andrea Bedini +9 more
doaj +2 more sources
Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures [PDF]
Nature Communications, 2022 DNA aptamers can activate insulin receptor as selective agonists or positive allosteric modulators. Here, authors determine structures of the insulin receptor bound to aptamers and provide a basis for the selective activation or allosteric regulation of ...
Junhong Kim +8 more
doaj +2 more sources
Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity [PDF]
Frontiers in PharmacologyIntroductionKratom (Mitragyna speciosa) contains over 50 alkaloids, yet the pharmacological activity of most remains poorly defined, limiting our understanding of its therapeutic potential and safety profile.MethodsWe conducted a comprehensive evaluation
S. E. Hemby +7 more
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Functional selectivity of GPCR-directed drug action through location bias. [PDF]
Nat Chem Biol, 2017 G-protein-coupled receptors (GPCRs) are increasingly recognized to operate from intracellular membranes as well as the plasma membrane. The β 2 -adrenergic GPCR can activate G s -linked cyclic AMP (G s -cAMP) signaling from endosomes.
Conti, Marco +6 more
core +4 more sources
Evaluation of Functional Selectivity of Haloperidol, Clozapine, and LASSBio-579, an Experimental Compound With Antipsychotic-Like Actions in Rodents, at G Protein and Arrestin Signaling Downstream of the Dopamine D2 Receptor [PDF]
Frontiers in Pharmacology, 2019 LASSBio-579, an N-phenylpiperazine antipsychotic lead compound, has been previously reported as a D2 receptor (D2R) ligand with antipsychotic-like activities in rodent models of schizophrenia.
Rafaela R. Silva +8 more
doaj +2 more sources
Kinetics of cytokine receptor trafficking determine signaling and functional selectivity [PDF]
eLife, 2019 Cytokines activate signaling via assembly of cell surface receptors, but it is unclear whether modulation of cytokine-receptor binding parameters can modify biological outcomes.
Jonathan Martinez-Fabregas +12 more
doaj +2 more sources