Assessment of structure-activity relationships and biased agonism at the Mu opioid receptor of novel synthetic opioids using a novel, stable bio-assay platform

• Published in: Biochemical pharmacology Vol. 177; p. 113910
• Main Authors: Vasudevan, Lakshmi, Vandeputte, Marthe, Deventer, Marie, Wouters, Elise, Cannaert, Annelies, Stove, Christophe P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.07.2020
• Subjects: Analgesics, Opioid - chemistry; Analgesics, Opioid - pharmacology; beta-Arrestin 2 - genetics; beta-Arrestin 2 - metabolism; Bio-assay; Biological Assay - methods; Flow Cytometry - methods; GTP-Binding Proteins - agonists; GTP-Binding Proteins - metabolism; HEK293 Cells; Humans; Mini-Gi; Mu opioid receptor; New psychoactive substances; Protein Interaction Maps; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Signal Transduction - drug effects; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Structure-Activity Relationship; Synthetic Drugs - chemistry; Synthetic Drugs - pharmacology; Thiophenes - chemistry; Thiophenes - pharmacology; Transduction, Genetic - methods; Transfection - methods; β-Arrestin; βarr; GRK; HEK293T; FDA; Gi; GTP; HM; SAR; CD8(TR); mini-Gi; NDA; cAMP; dNGFR; EGFP; LgBiT; AUC; NPS; SD; Trp; BV; NanoBiT; SmBiT; Emax; Asp; AC; pEC50; β-Arrestin; NSO; Mu opioid receptor; GTPγ[35S]; MOR; CB1; His; APC; GPCR; TM; GIRK; SEM; New psychoactive substances; Bio-assay; Mini-Gi

[Display omitted] Fentanyl and morphine are agonists of the Mu opioid receptor (MOR), which is a member of the GPCR family. Their analgesic effects are associated with unwanted side effects. On a signaling level downstream from MOR, it has been hypothesized that analgesia may be mediated through the...