Structure-signal relationships at κ-opioid receptor (KOR) revealed by bicyclo[2.2.2]octene enamide derivatives.
κ-Opioid receptor (KOR) agonists are promising candidates for analgesic development, yet their clinical application is limited by on-target adverse effects such as sedation and dysphoria. Attenuating β-arrestin2 recruitment while retaining G-protein signaling has therefore attracted interest as a strategy for improving...