| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MCOPPB targets the N/OFQ peptide (NOP) receptor (also known as ORL1 receptor). Binding affinities (Ki): hNOP 0.0858 nM, human μ-opioid receptor 1.052 nM, human κ-opioid receptor 23.1 nM, human δ-opioid receptor >667 nM [1].
Functional activities (EC50 for [35S]GTPγS binding): hNOP 0.39 nM (Emax=140%), μ 34 nM (Emax=30%), κ 80 nM (Emax=43%), δ 4596 nM (Emax=79%) [1]. Selectivity ratios: μ/hNOP=12.26, κ/hNOP=269, δ/hNOP>7770 [1]. |
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| ln Vitro |
MCOPPB showed potent in vitro binding affinity to human NOP receptor with Ki = 0.0858 nM, and potent functional agonism with EC50 = 0.39 nM and Emax = 140% (relative to N/OFQ) in [35S]GTPγS binding assay. It exhibited high selectivity over μ, κ, and δ opioid receptors (Ki values 1.052 nM, 23.1 nM, and >667 nM respectively; EC50 values 34 nM, 80 nM, and 4596 nM respectively). The compound acted as a full NOP agonist with greater maximal effect than N/OFQ. [1]
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| ln Vivo |
MCOPPB demonstrated high oral NOP receptor occupancy in mouse brain: 53 ± 5.9% at 10 mg/kg po after 1 hour (ex vivo displacement of [3H]N/OFQ binding). It also showed significant oral anxiolytic efficacy in the Vogel anticonflict test in mice at a minimum effective dose of 10 mg/kg po. [1]
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| Enzyme Assay |
The NOP receptor binding assay was performed using human NOP receptor-expressing HEK-293 cell membranes. Membranes (8.3 μg) were incubated with 0.4 nM [3H]N/OFQ, 1.0 mg WGA-SPA beads, and six different concentrations of test compound (10^-11 to 10^-5 M, 10-fold) in 0.2 mL of 50 mM HEPES buffer (pH 7.4) containing 10 mM MgCl2 for 45 min at 22°C. Non-specific binding was determined with 1 μM unlabeled N/OFQ. After centrifugation at 1000 rpm for 1 min, radioactivity was measured by a liquid scintillation counter. IC50 values were calculated by nonlinear regression, and Ki values were calculated using the Cheng-Prusoff equation: Ki = IC50/(1+[L]/KD). The KD for [3H]N/OFQ was 0.135 nM. [1]
The [35S]GTPγS functional assay was performed using human NOP, μ, κ, or δ receptor-expressing cell membranes. Membranes (same amount as for binding assays) were suspended in assay buffer (20 mM HEPES, 100 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 μM GDP, 1 mM DTT, pH 7.4). They were incubated with 0.4 nM [35S]GTPγS, 1.5 mg WGA-SPA beads, and various concentrations of test compound in 0.2 mL total volume for 30 min at 22°C. Non-specific binding was assessed with 10 μM unlabeled GTPγS. Agonist-stimulated binding was determined as the difference between total binding in the presence of compound and basal binding in the absence of compound. EC50 (potency) and Emax (efficacy, as % of control agonist maximum) were calculated by nonlinear regression. Control agonists: N/OFQ for NOP, DAMGO for μ, enadoline for κ, DPDPE for δ. [1] |
| Animal Protocol |
For ex vivo NOP occupancy study: Male ddY mice (5-6 weeks) were deprived of water for 24 h, then given MCOPPB orally at 10 mg/kg (suspended in 0.1% methylcellulose solution, volume 0.1 mL/10 g body weight). After 1 h, whole brains were removed; cerebellum and medulla were discarded. Brain tissues were homogenized in ice-cold 50 mM Tris-HCl buffer (pH 7.4) containing 1 mM EDTA, 10 mM MgCl2, and 320 mM sucrose. Homogenates were centrifuged at 1000 rpm for 10 min, supernatants combined and centrifuged at 38,000×g for 30 min. Pellets were resuspended and centrifuged again, then final pellets suspended in buffer containing 320 mM sucrose. Membranes (160 μg protein) were incubated with 0.3 nM [3H]N/OFQ in 50 mM HEPES buffer (pH 7.4) with 1 mM EDTA and 10 mM MgCl2 for 30 min at 25°C. Reaction was terminated by rapid filtration through glass fiber filters, and radioactivity measured. Specific binding was determined by subtracting binding in presence of 1 μM N/OFQ. All assays in triplicate. Occupancy was calculated as % displacement of specific [3H]N/OFQ binding compared to vehicle control. [1]
For Vogel anticonflict test: Mice were given MCOPPB orally at 10 mg/kg (minimum effective dose), and significant anticonflict activity was observed. Detailed protocol not provided in this article. [1] |
| ADME/Pharmacokinetics |
MCOPPB demonstrated brain penetration after oral administration. In an ex vivo binding study in mice, oral administration of MCOPPB at 10 mg/kg resulted in 53 ± 5.9% inhibition of NOP receptor specific binding in the brain 1 hour post-dose. No other pharmacokinetic parameters (e.g., half-life, oral bioavailability, clearance, volume of distribution) were reported in this study. [1]
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| Toxicity/Toxicokinetics |
At the anxiolytic dose (10 mg/kg p.o.), MCOPPB did not cause locomotor impairment, memory deficits, or ethanol-induced hypnosis. [1]
At a higher dose (30 mg/kg p.o.), MCOPPB still did not impair memory or induce ethanol interaction; however, at 50 mg/kg p.o., a non-significant decrease in locomotor activity was observed and significant enhancement of ethanol-induced hypnosis occurred (4/8 mice, p<0.05). [1] No myorelaxant, ataxic, or sedative effects were noted at anxiolytic doses. Diazepam, in contrast, produced memory deficits and enhanced ethanol-induced hypnosis. [1] |
| References |
J Pharmacol Sci.2008 Mar;106(3):361-8;J Med Chem.2009 Feb 12;52(3):610-25.
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| Additional Infomation |
MCOPPB is a novel non-peptide NOP receptor full agonist developed as an orally potent anxiolytic. It was identified through structure-activity relationship studies of 1,2-disubstituted benzimidazole derivatives. The compound possesses favorable physicochemical properties for brain penetration: molecular weight 408.62, TPSA 33.09 Ų, ACDlogD7.4 2.57, hydrogen bond donors 1, acceptors 3, rotatable bonds 3. It shows differentiation from benzodiazepine anxiolytics (e.g., diazepam) in terms of potential side effects. Further pharmacological characterization and comparisons with diazepam are reported elsewhere (Hayashi et al., 2006; Hirao et al., 2008). [1]
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| Molecular Formula |
C26H43CL3N4
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| Molecular Weight |
518.01
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| Exact Mass |
516.255
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| CAS # |
1108147-88-1
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| Related CAS # |
1108147-88-1(HCl);1028969-49-4;
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| PubChem CID |
25208093
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| Appearance |
White to off-white solid powder
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| LogP |
8.315
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
33
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| Complexity |
535
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1(N2CCC(N3C4=CC=CC=C4N=C3[C@H]5CNCCC5)CC2)CCCCCCC1.[H]Cl.[H]Cl.[H]Cl
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| InChi Key |
DTIPEVOPCGEULQ-RFCADEKQSA-N
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| InChi Code |
InChI=1S/C26H40N4.3ClH/c1-26(15-7-3-2-4-8-16-26)29-18-13-22(14-19-29)30-24-12-6-5-11-23(24)28-25(30)21-10-9-17-27-20-21;;;/h5-6,11-12,21-22,27H,2-4,7-10,13-20H2,1H3;3*1H/t21-;;;/m1.../s1
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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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 | 1.9305 mL | 9.6523 mL | 19.3046 mL | |
| 5 mM | 0.3861 mL | 1.9305 mL | 3.8609 mL | |
| 10 mM | 0.1930 mL | 0.9652 mL | 1.9305 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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