KOR agonist 7 (Compound 29) is a highly selective kappa-opioid receptor (KOR) agonist with a Ki of 138 nM. KOR agonist 7 shows no activity at µ- and delta-opioid receptors or sigma1 receptor, and exhibits extremely low affinity for sigma2 receptor (Ki = 2.8 µM). KOR agonist 7 significantly reduces the secretion of pro-inflammatory cytokines such as IL-6, TNF-alpha, and IFN-gamma, while increasing the production of the anti-inflammatory cytokine IL-10. KOR agonist 7 downregulates the expression of the pro-inflammatory M1 macrophage marker CD80 and upregulates the anti-inflammatory M2 macrophage marker CD163. KOR agonist 7 holds potential for applications in analgesia and immune modulation[1].
