JTC-801 HCl 244218-51-7_Opioid Receptor_GPCR & G Protein_Signaling Pathways_Products

JTC-801 HCl (JTC 801; JTC801), the hydrochloride salt of JTC801, is a potent, orally bioactive and selective opioid receptor-like1 (ORL1) receptor antagonist with potential analgesic activity. It blocks opioid receptor-like1 (ORL1) with an IC50 of 94 nM.

Physicochemical Properties

Molecular Formula

C26H26CLN3O2

Molecular Weight

447.96

Exact Mass

447.171

Elemental Analysis

C, 69.71; H, 5.85; Cl, 7.91; N, 9.38; O, 7.14

CAS #

244218-51-7

Related CAS #

244218-51-7

PubChem CID

5311339

Appearance

White to off-white solid powder

Boiling Point

580.9ºC at 760mmHg

Melting Point

235℃

Flash Point

305.1ºC

Vapour Pressure

1.73E-13mmHg at 25°C

LogP

6.975

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

577

Defined Atom Stereocenter Count

SMILES

Cl[H].O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])[H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1C(N([H])C1C([H])=C([H])C2C(=C(C([H])=C(C([H])([H])[H])N=2)N([H])[H])C=1[H])=O

InChi Key

NQLIYKXNAXKMBL-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H25N3O2.ClH/c1-3-18-8-11-21(12-9-18)31-16-19-6-4-5-7-22(19)26(30)29-20-10-13-25-23(15-20)24(27)14-17(2)28-25;/h4-15H,3,16H2,1-2H3,(H2,27,28)(H,29,30);1H

Chemical Name

N-(4-amino-2-methylquinolin-6-yl)-2-[(4-ethylphenoxy)methyl]benzamide;hydrochloride

Synonyms

JTC-801; JTC 801; JTC801HCl

HS Tariff Code

2934.99.9001

Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets

NOP Receptor/ORL1

ln Vitro

In vitro activity: JTC-801 exhibits selectivity for the ORL1 receptor (Ki = 8.2 nM) over the μ, κ, and δ opioid receptors by approximately 12.5, 129, and 1055 folds, respectively. In human ORL1 receptor-expressing HeLa cells, JTC-801 does not inhibit the accumulation of cyclic AMP stimulated by forskolin; however, it does inhibit the accumulation of cyclic AMP inhibited by nociceptin, suggesting that JTC-801 has complete antagonistic activity.[2] JTC-801 inhibits the μ-receptor with an IC50 of 1831 nM and the ORL1 receptor with an IC50 of 472 nM in the rat cerebrocortical membrane. With an IC50 of 2.58 μM, JTC-801 completely counteracts the suppression of nociceptin on forskolin-induced cyclic AMP accumulation in HeLa cells expressing the ORL1 receptor.[1]

ln Vivo

JTC-801 (0.3–3 mg/kg) administered orally counteracts nociceptin-induced allodynia in mice and exhibits analgesic effects in rats and mice in a formalin test and hot plate test.[2] JTC-801 prolongs the exposed heat stimulus or escape response latency (ERL) in the mouse hot-plate test at minimum effective doses (MED) of 0.01 mg/kg by intravenous injection or 1 mg/kg by po. Using a MED of 0.01 mg/kg71 by intravenous injection or 1 mg/kg by po, JTC-801 decreases the nociceptive response in both the first and second phases in the rat formalin test.[1] In a dose-dependent manner, JTC-801 restores paw withdrawal latency (PWL). JTC-801 inhibits an increase in osteoclast numbers but not the decline in bone mineral content (BMC) or bone mineral density (BMD) brought on by a chronic constriction injury (CCI).[3] Both systemic (3-30 mg/kg) and spinal (22.5 and 45 pg) JTC-801 reverse tactile allodynia caused by L5/L6 spinal nerve ligation in a dose-dependent manner. Moreover, Fos-like immunoreactivity in the spinal cord's dorsal horn (laminae I/II) is decreased by systemic JTC-801.[4] JTC-801 has an ED50 of 0.83 mg/kg and 1.02 mg/kg for mechanical and cold anti-allodynic effects, respectively, that are dose-dependent.[6]

Enzyme Assay

Membranes from human μ-opioid receptor-expressing CHO-K1 cells suspended in 50 mM Tris-HCl buffer (pH 7.4) with 10% sucrose, 5 mM MgCl₂, and 0.33 nM ²H-labeled diprenorphine are incubated for 2.5 hours at room temperature with different concentrations of JTC-801. Whatman 934-AH is used to filter the membranes, and a TopCount A9912V scintillation counter is used to count radioactivity. 10 μM naloxone is used to measure nonspecific binding (6.4%). By deducting nonspecific binding from total binding, specific binding is computed. The mean±SE (n=3) is the data.

Animal Protocol

The anti-nociceptive effect of JTC-801 and morphine is tested using the formalin stimulation test to determine the antagonistic effect of naloxone, a non-specific opioid antagonist. The procedure involves injecting 50 μL of 5% formalin subcutaneously into each rat's left hind limb to cause a licking response. Immediately following the formalin injection, the first five minutes are referred to as the first phase, and the next 15 minutes are referred to as the second phase. A measure of pain is taken of how long a limb is licked during each phase. Naloxone (10 mg/kg) dissolved in physiological saline is administered subcutaneously fifteen minutes prior to the formalin injection. JTC-801 and morphine, dissolved in 5% sorbitol and injected into the tail vein at doses of 0.03 and 1.0 mg/kg, respectively, five minutes prior to the formalin injection. An oral dose of 3.0 mg/kg of JTC-801 and 30 mg/kg of morphine is given 60 minutes prior to the formalin injection.

References

[1]. Br J Pharmacol . 2002 Jan;135(2):323-32.

[2]. J Med Chem . 2000 Nov 30;43(24):4667-77.

[3]. Neurosci Lett . 2003 Nov 20;351(3):133-6.

[4]. Eur J Pharmacol . 2005 Mar 14;510(3):223-8.

[5]. Neuropeptides . 2007 Aug;41(4):239-47.

[6]. Pharmacol Biochem Behav . 2011 Oct;99(4):540-4.

Solubility Data

Solubility (In Vitro)

DMSO: 90~100 mg/mL (200.9~223.2 mM)

Water:< 1 mg/mL

Ethanol: ~31 mg/mL (~69.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 0.5% methylcellulose: 30 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2323 mL	11.1617 mL	22.3234 mL
	5 mM	0.4465 mL	2.2323 mL	4.4647 mL
	10 mM	0.2232 mL	1.1162 mL	2.2323 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

PeptideDB

JTC-801 HCl 244218-51-7

CAS No.: 244218-51-7

Physicochemical Properties

Biological Activity

Solubility Data