product name JTC-801
Description: JTC-801 is a potent, orally active and selective opioid receptor-like1 (ORL1) receptor antagonist with IC50 of 94 nM, it weakly inhibits receptors δ, κ, and μ. JTC-801 is an opioid analgesic drug used in scientific research. JTC-801 is also a selective antagonist for the nociceptin receptor, also known as the ORL-1 receptor. The noiciceptin receptor has complex effects which are involved in many processes involved in pain and inflammation responses, and activation of this receptor can either increase or reduce pain depending on dose.
References: Br J Pharmacol. 2002 Jan;135(2):323-32; J Med Chem. 2000 Nov 30;43(24):4667-77.
447.96
Formula
C26H25N3O2.HCl
CAS No.
244218-51-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 90 mg/mL (200.9 mM)
Water: < 1 mg/mL
Ethanol: 31 mg/mL (69.2 mM)
Solubility (In vivo)
0.5% methylcellulose: 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. |
