ML138

ML138 is a blood-brain barrier-permeable κ-opioid receptor (KOR) agonist, with an EC₅₀ value of 0.87 μM and a human K_i value of 2.4 nM for human receptors; it exhibits high selectivity for KOR over μ, δ and other receptors. ML138 activates β-arrestin (beta-arrestin)-mediated signaling pathways, stimulates G protein coupling, and activates the downstream extracellular regulated protein kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAP kinase) signaling pathway. ML138 is applicable to research related to addictive behaviors^[1][2]. In Vitro:ML138 acts as a κ-opioid receptor agonist in the KOR DiscoveRx β-arrestin PathHunter cell assay, with an EC₅₀ of 0.87 μM^[1].
ML138 acts as a κ-opioid receptor (KOR) agonist in cellular assays based on high-content imaging of β-arrestin translocation mediated by κ-opioid receptors, with an EC₅₀ of 0.35 μM, and exhibits over 100-fold selectivity over MOR and DOR^[1].
ML138 binds to the κ-opioid receptor with high affinity (K_i = 2.4 nM), exhibits over 792-fold selectivity for MOR and over 2000-fold selectivity for DOR, and shows weak binding to 11 non-opioid targets^[1].
ML138 (10 µM; 1.5 h) inhibits κ-opioid receptor activity in OPRK1 β-arrestin cells, with an IC₅₀ of 870 nM^[2].
ML138 activates cells expressing KOR, with an EC₅₀ of 350 nM in the HCS-Transfluor assay^[2].
ML138 binds potently and selectively to the κ-opioid receptor with a K_i value of 0.23 nM, exhibiting over 2100-fold selectivity over μ and δ-opioid receptors, and over 5000-fold selectivity over weakly bound off-target GPCRs^[2].
ML138 stimulates the coupling of G proteins to κ-opioid receptors, with an EC₅₀ of 55.2 nM^[2].
ML138 stimulates ERK1/2 phosphorylation in cells expressing κ-opioid receptors^[2].