| Identification | Back Directory | [Name]
6aH-6,14a-(Iminoethano)naphth[2,1-b]acridine-2,6a-diol, 5,6,7,14-tetrahydro-17-methyl-, (6R,6aS,14aR)- | [CAS]
1256921-89-7 | [Synonyms]
KNT127
KNT-127
KNT 127
6aH-6,14a-(Iminoethano)naphth[2,1-b]acridine-2,6a-diol, 5,6,7,14-tetrahydro-17-methyl-, (6R,6aS,14aR)- | [Molecular Formula]
C24H24N2O2 | [MOL File]
1256921-89-7.mol | [Molecular Weight]
372.46 |
| Chemical Properties | Back Directory | [Melting point ]
250-254 °C (decomp) | [Boiling point ]
594.7±50.0 °C(Predicted) | [density ]
1.38±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
9.87±0.40(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
KNT-127 is a δ-Opioid receptor agonist. | [Uses]
KNT-127 is a potent δ-opioid receptor agonist that crosses the blood-brain barrier (BBB). KNT-127 is highly selective to the δ receptor, with Ki values of 0.16, 21.3 and 153 nM for δ, μ and κ receptors, respectively. KNT-127 increases the release of dopamine and L-glutamate in the striatum, nucleus accumbens, and prefrontal cortex. KNT-127 has analgesic, antidepressant and antianxiety activities[1][2][3][4][5]. | [in vivo]
KNT-127 (10 mg/kg; Subcutaneous injection; Single dose) exerts antidepressant effects through Akt-mTORC1-p70S6K signaling pathway in medial prefrontal cortex and ERK-mTORC1-p70S6K signaling pathway in amygdala[1].
KNT-127 (20 mg/kg; Intraperitoneal injection; 38 days) has an improved effect in mouse models of depression[2].
KNT-127 (5 mg/kg; Subcutaneous injection; Single dose) has an improved effect in mouse models of chronic migraine[3]. | Animal Model: | Chronic vicarious social defeat stress (cVSDS) treated male C57BL/6J mice[2] | | Dosage: | 20 mg/kg | | Administration: | Intraperitoneal injection (i.p.); 38 days | | Result: | Improved decreased social interaction behaviors and increased serum corticosterone levels.
Suppressed decreases in the hippocampal newborn neuron survival rate.
Inhibited cVSDS-induced overactivation of microglia.
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| Animal Model: | Nitroglycerin treated C57BL6/J mice[3] | | Dosage: | 5 mg/kg | | Administration: | Subcutaneous injection (s.c.); Single dose | | Result: | Did not alter mechanical responses in vehicle pre-treated mice.
Inhibited Nitroglycerin-induced chronic allodynia.
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| [IC 50]
δ Opioid Receptor/DOR; mTORC1 | [References]
[1] Yoshioka T, et al. Delta opioid receptor agonists activate PI3K-mTORC1 signaling in parvalbumin-positive interneurons in mouse infralimbic prefrontal cortex to exert acute antidepressant-lie effects. Mol Psychiatry. 2024 Dec 6. DOI:10.1038/s41380-024-02814-z
[2] Yoshioka T, et al. KNT-127, a selective delta opioid receptor agonist, shows beneficial effects in the hippocampal dentate gyrus of a chronic vicarious social defeat stress mouse model. Neuropharmacology. 2023 Jul 1;232:109511. DOI:10.1016/j.neuropharm.2023.109511
[3] Bertels Z, et al. A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia. Headache. 2021 Jan;61(1):170-178. DOI:10.1111/head.14019
[4] Nagase H, et al. Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration. Bioorg Med Chem Lett. 2010;20(21):6302-6305. DOI:10.1016/j.bmcl.2010.08.083
[5] Tanahashi S, et al. Novel δ1-receptor agonist KNT-127 increases the release of dopamine and L-glutamate in the striatum, nucleus accumbens and median pre-frontal cortex. Neuropharmacology. 2012;62(5-6):2057-2067. DOI:10.1016/j.neuropharm.2012.01.005 |
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