| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
ORL1 (opioid receptor-like 1, also known as nociceptin receptor NOP). JTC-801 also shows weak inhibitory effects on human δ receptors (IC50 >10 μM), κ receptors (IC50 >10 μM), and μ receptors (IC50 = 325 nM).
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| ln Vitro |
JTC-801, with an IC50 value of 94±8.6 nM, inhibits the binding of [3H]-nociceptin (50 pM) to the ORL1 receptor expressed in HeLa cells. JTC-801 has a mild inhibitory effect on ligand binding to human delta receptors (IC50>10 μM), kappa receptors (IC50>10 μM), and μ receptors (IC50=325 nM). JTC-801 inhibits both u receptors (IC50=1831 nM) and ORL1 receptors (IC50=472 nM) in rat cerebral cortex membranes. When nociceptin was used at a dose of 1 nM, JTC-801 at 10 μM abolished its inhibitory action on forskolin-induced increases in cyclic AMP levels (IC50: 2.58 μM). Cyclic AMP synthesis cannot be impacted by JTC-801 alone[1]. JTC-801 has the following affinities: 8.2 nM, 102.9 nM, 1057.5 nM, and 8647.2 nM for the ORL1 receptor and the human opioid u-, κ-, and δ-receptors, respectively [2].
JTC-801 inhibits [³H]-nociceptin (50 pM) binding to ORL1 receptor expressed in HeLa cells with an IC50 of 94±8.6 nM. It completely antagonizes nociceptin-induced suppression of forskolin-stimulated cAMP accumulation in ORL1-expressing HeLa cells with an IC50 of 2.58 μM. JTC-801 alone does not affect cAMP synthesis. |
| ln Vivo |
JTC-801 (≥0.01 mg/kg, iv or 1 mg/kg, po) inhibits the allodynia that nociceptin causes in mice. JTC-801 extended the escape response latency (ERL) of thermal stimuli exposure in the mouse hot plate test at a minimum effective dose (MED) of 1 mg/kg oral in the rat formalin test or 0.01 mg/kg intravenously. JTC-801, when administered intravenously at a MED of 0.01 mg/kg and orally at a MED of 1 mg/kg, decreased both phase I and phase II nociceptive responses. Naloxone (10 mg/kg, sc) had no effect on JTC-801's antinociceptive action. Whether given intravenously or orally, JTC-801 has strong antinociceptive effects and antagonizes responses of ORL1 receptors in animal models of acute pain [1]. JTC -801 (0.3 mg/kg) lessens the allodynia that mice experience after receiving a nociceptin intrathecal injection [2]. The effects of SPS on mechanical allodynia, thermal hyperalgesia, anxiety-like behavior, and hypercortisolism are reversed by JTC-801 (6 mg/kg ip once daily). JTC -801 therapy also reversed the increase of NOP receptor protein and mRNA in the amygdala and PAG. JTC -801 inhibits high N/OFQ levels in serum, CSF, PAG and hippocampus on day 21 of SPS [3]. Through writhing test and tail flick test, JTC-801 (0.05-5 mg/kg, ip) decreases the analgesic effect of N2O on 129Sv mice [4].
JTC-801 (≥0.01 mg/kg, i.v. or 1 mg/kg, p.o.) antagonizes nociceptin-induced allodynia in mice. In the mouse hot-plate test, it prolongs escape response latency with minimum effective doses of 0.01 mg/kg (i.v.) and 1 mg/kg (p.o.). In the rat formalin test, it reduces both phases of nociceptive response with MED of 0.01 mg/kg (i.v.) or 1 mg/kg (p.o.). This antinociceptive action is not inhibited by naloxone. |
| Enzyme Assay |
[³H]-Nociceptin binding assay: HeLa cells expressing human ORL1 receptors are incubated with 50 pM [³H]-nociceptin and varying concentrations of JTC-801 at room temperature for 60 min. Nonspecific binding is determined using excess unlabeled nociceptin. Bound radioactivity is measured by rapid filtration through glass fiber filters and liquid scintillation counting. IC50 is calculated from competition curves.
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| Cell Assay |
cAMP accumulation assay: HeLa cells stably expressing ORL1 receptors are pre-incubated with JTC-801 at various concentrations for 15 min, then stimulated with forskolin (10 μM) in the presence or absence of nociceptin (1 nM) for 30 min at 37°C. Intracellular cAMP levels are measured using a cAMP ELISA or RIA kit. The IC50 for antagonism of nociceptin-induced cAMP suppression is calculated.
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| Animal Protocol |
Mouse hot-plate test: Mice are treated with JTC-801 (i.v. or p.o.) and placed on a 55°C hot plate. Escape response latency is recorded with a 30 sec cutoff. Mouse allodynia model: Nociceptin is administered intracerebroventricularly to induce allodynia, and JTC-801 is given i.v. or p.o. prior to nociceptin. Paw withdrawal threshold to von Frey filaments is measured. Rat formalin test: Rats receive formalin injection into the hind paw after JTC-801 administration; licking/biting time is recorded in early (0-5 min) and late (15-60 min) phases.
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| ADME/Pharmacokinetics |
JTC-801 shows oral bioavailability with efficacious antinociceptive effects via both intravenous and oral administration. Minimum effective doses are 0.01 mg/kg (i.v.) and 1 mg/kg (p.o.) in multiple pain models. The compound is orally bioactive. Detailed pharmacokinetic parameters such as half-life, Cmax, and AUC have not been extensively reported in the literature.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published in the available literature. JTC-801 is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
N-(4-amino-2-methyl-6-quinolinyl)-2-[(4-ethylphenoxy)methyl]benzamide is an aminoquinoline compound. It is a nociceptor receptor antagonist and analgesic, and has been evaluated for use in cancer treatment.
JTC-801 is a selective antagonist for the nociceptin receptor (ORL-1/NOP). The nociceptin receptor is involved in pain and inflammatory responses, and its activation can either increase or reduce pain depending on dose. JTC-801 has the following binding affinities (Ki): 8.2 nM for ORL1, 102.9 nM for human μ, 1057.5 nM for κ, and 8647.2 nM for δ receptors. It represents a new class of analgesics acting via ORL1 antagonism. |
| Molecular Formula |
C26H25N3O2
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|---|---|
| Molecular Weight |
411.5
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| Exact Mass |
411.195
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| CAS # |
244218-93-7
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| Related CAS # |
244218-93-7
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| PubChem CID |
5311340
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| Appearance |
White to off-white solid powder
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| LogP |
6.484
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
577
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VTGBZWHPJFMTKS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H25N3O2/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)
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| Chemical Name |
N-(4-amino-2-methylquinolin-6-yl)-2-((4-ethylphenoxy)methyl)benzamide
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| Synonyms |
JTC-801 free base; JTC-801; Related CAS#: 244218-93-7
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4301 mL | 12.1507 mL | 24.3013 mL | |
| 5 mM | 0.4860 mL | 2.4301 mL | 4.8603 mL | |
| 10 mM | 0.2430 mL | 1.2151 mL | 2.4301 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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