KOR agonist 6 

KOR agonist 6 is a KOR agonist (K_i = 0.25 pM). KOR agonist 6 shows agonistic activity at MOR and DOR in CHO cells and inhibits Forskolin (HY-15371)-stimulated cAMP accumulation. KOR agonist 6 stimulates KOR-mediated [³⁵S]GTPγS binding and inhibits cAMP accumulation in KOR-expressing HEK293 cells with potent agonistic activity, while showing lower β-arrestin recruitment potency. KOR agonist 6 demonstrates anti-nociceptive efficacy in mice. KOR agonist 6 can be used for the study of analgesics with reduced central nervous system (CNS) side effects^[1].

KOR agonist 6 (Compound 5i) exhibits ultra-high binding affinity to κ-opioid receptor (KOR (K_i = 0.00025 nM)) and exceptional subtype selectivity over μ-opioid receptor (MOR (K_i = 14.1 nM)) and δ-opioid receptor (DOR (K_i = 120.7nM))^[1].
KOR agonist 6 shows agonistic activity at MOR (EC₅₀ = 44.78 nM, E_max = 88.71%) and DOR (EC₅₀ = 15.26 nM, E_max = 85.16%) in CHO cells and inhibits Forskolin (HY-15371)-stimulated cAMP accumulation (EC₅₀ = 200.3 nM, E_max = 99.51%)^[1].
KOR agonist 6 stimulates KOR-mediated [³⁵S]GTPγS binding with potent activity (EC₅₀ = 0.024 nM, E_max = 106.9%) in KOR-expressing cell membranes, inhibits cAMP accumulation in KOR-expressing HEK293 cells with ultra-potent agonistic activity (EC₅₀ = 0.43 pM, E_max = 63.63%) and induces β-arrestin recruitment in KOR-Tango plasmid-transfected HTLA cells with lower potency (EC₅₀ = 0.143 nM, E_max = 42.89%)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

KOR agonist 6 (Compound 5i) (0.4-8.0 mg/kg, i.p., detected at 6 h post-administration) demonstrates dose-dependent antinociceptive efficacy in mice hot plate test (ED₅₀ = 0.6 mg/kg)^[1].
KOR agonist 6 (0.08-8.0 mg/kg, i.p., detected at 6 h post-administration) exerts dose-dependent antinociceptive activity in mice abdominal constriction test(ED₅₀ = 1.5 mg/kg)^[1].
KOR agonist 6 (0.8-8.0 mg/kg, i.p., conditioned for 6 days, tested on day 8 with 15 min free exploration) shows no significant conditioned place aversion in male CD1 mice^[1].
KOR agonist 6 (0.8-8.0 mg/kg, i.p., monitored for 1 h at 6 h post-administration) does not cause significant reduction in spontaneous locomotor activity (total moving distance) in male Kunming mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

580.72

C₃₅H₄₀N₄O₄

O=C(NC1=CC=C([C@H]2C[C@@]34CC[C@]2(OC)[C@H]5[C@]36C7=C(C(OC)=CC=C7CC4N(CC6)CC8CC8)O5)C=C1)C9=NN(C=C9)C

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• [1]. Kong L, et al. Structure-Activity Relationship of N-Cyclopropylmethyl-7α-[para-(arylcarboxamido)phenyl]-6,14-endoethano-tetrahydronorthebaines as Potent and Selective Kappa Opioid Receptor Agonists. J Med Chem. 2025 Aug 14;68(15):15889-15909.  [Content Brief]