product name ADL5859 HCl
Description: ADL5859 HCl is a potent, orally bioavailable δ-opioid receptor agonist with Ki of 0.8 nM, it has displayed selectivity against opioid receptor κ, μ, and weak inhibitory activity at the hERG channel. ADL5859 agonizes δ-opioid receptor with a 1000-fold selectivity than µ- or κ-opioid receptor with Ki of 32 nM and 37 nM, respectively.
References: J Med Chem. 2008 Oct 9;51(19):5893-6; J Pharmacol Exp Ther. 2012 Sep;342(3):799-807.
428.95
Formula
C24H28N2O3.HCl
CAS No.
850173-95-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 86 mg/mL (200.5 mM)
Water: 5 mg/mL (11.6 mM)
Ethanol: 1 mg/mL (2.3 mM)
Solubility (In vivo)
0.5% hydroxyethyl cellulose+0.1% Tween 80: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: JTC-801 displays about 12.5-, 129-, and 1055-fold selectivity for ORL1 receptor (Ki = 8.2 nM) over μ-, κ-, and δ-opioid receptors, respectively. JTC-801 does not inhibit forskolin-stimulated cyclic AMP accumulation in human ORL1 receptor-expressing HeLa cells, but it prevents nociceptin-induced inhibition of cyclic AMP accumulation, indicating that JTC-801 possesses full antagonistic activity. In rat cerebrocortical membrane, JTC-801 inhibits ORL1 receptor with IC50 of 472 nM and μ-receptor with IC50 of 1831 nM. JTC-801 completely antagonizes the suppression of nociceptin on forskolin-induced accumulation of cyclic AMP with IC50 of 2.58 μM in HeLa cells expressing ORL1 receptor. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Oral administration of JTC-801 (0.3-3 mg/kg) antagonizes nociceptin-induced allodynia in mice, and shows analgesic effect in a hot plate test using mice and in a formalin test using rats. In mouse hot-plate test, JTC-801 prolongs escape response latency (ERL) or exposed heat stimulus with minimum effective doses (MED) of 0.01 mg/kg by i.v. or 1 mg/kg by p.o. In the rat formalin test, JTC-801 reduces both the first and second phases of the nociceptive response with MED of 0.01 mg/kg71 by i.v. or 1 mg/kg by p.o. JTC-801 dose-dependently normalizes paw withdrawal latency (PWL). Although JTC-801 does not inhibit a chronic constriction injury (CCI)-induced decrease in bone mineral content (BMC) and bone mineral density (BMD), it inhibits an increase in the number of osteoclasts. Tactile allodynia induced by L5/L6 spinal nerve ligation is reversed by both systemic (3-30 mg/kg) and spinal (22.5 and 45 pg) JTC-801 in a dose-dependent manner. Furthermore, systemic JTC-801 reduces Fos-like immunoreactivity in the dorsal horn of the spinal cord (laminae I/II). JTC-801 produces dose-dependent mechanical and cold anti-allodynic effects with ED50 of 0.83 mg/kg and 1.02 mg/kg, respectively. |
| Animal model | Male ICR (CD-1) subjected to nociceptin-induced allodynia test or hot plate test, and Male SD rats subjected to formalin-induced paw-licking response |
| Formulation & Dosage | Suspended in 0.5% methyl cellulose solution or dissolved in 5% sorbitol; 10 mg/kg; oral or i.v. injection |
| References | Br J Pharmacol. 2002 Jan;135(2):323-32; J Med Chem. 2000 Nov 30;43(24):4667-77. |
