| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
hY5 receptor ( Ki = 8 nM ); hY1 receptor ( Ki = 16032 nM )
NTNCB hydrochloride is a neuropeptide Y Y5 (NPY Y5) receptor antagonist. The representative compound (sulfonamide 11) described in the literature has a Ki of 8 nM for the human Y5 receptor (hY5) and exhibits high selectivity over other NPY receptor subtypes (e.g., Ki for hY1 > 16,000 nM). [1] |
|---|---|
| ln Vitro |
In radioligand binding assays using membranes from COS-7 cells transiently transfected with NPY receptor subtypes, NTNCB hydrochloride (represented by sulfonamide 11) demonstrated high affinity for the hY5 receptor with a Ki of 8 nM. [1]
In functional assays using HEK-293 or LMTK- cells stably transfected with NPY receptor subtypes, NTNCB hydrochloride acted as a pure antagonist. It competitively attenuated the ability of NPY to inhibit forskolin-stimulated cAMP production, with a Kb value (26 nM for hY5) similar to its Ki. [1] Selectivity screening against a panel of G protein-coupled receptors (GPCRs) revealed that NTNCB hydrochloride (sulfonamide 11) is selective for the hY5 receptor (>100-fold for most receptors), with main cross-reactivity observed at the human α2c (Ki = 100 nM) and D2 (Ki = 63 nM) receptors. [1] In radioligand binding assays using membranes from COS-7 cells transiently transfected with NPY receptor subtypes, NTNCB hydrochloride (represented by sulfonamide 11) demonstrated high affinity for the hY5 receptor with a Ki of 8 nM. [1] In functional assays using HEK-293 or LMTK- cells stably transfected with NPY receptor subtypes, NTNCB hydrochloride acted as a pure antagonist. It competitively attenuated the ability of NPY to inhibit forskolin-stimulated cAMP production, with a Kb value (26 nM for hY5) similar to its Ki. [1] Selectivity screening against a panel of G protein-coupled receptors (GPCRs) revealed that NTNCB hydrochloride (sulfonamide 11) is selective for the hY5 receptor (>100-fold for most receptors), with main cross-reactivity observed at the human α2c (Ki = 100 nM) and D2 (Ki = 63 nM) receptors. [1] |
| Enzyme Assay |
Radioligand binding assays were performed using membranes prepared from COS-7 cells that had been transiently transfected with cDNA encoding human NPY receptor subtypes (Y1, Y2, Y4, Y5). The assays utilized ¹²⁵I-labeled peptide YY (PYY) as the radioligand. Various concentrations of test compounds were incubated with the membrane preparations and radioligand to generate competition binding curves. Ki values were calculated from these curves to determine binding affinity. [1]
Functional antagonist activity was assessed using a cAMP accumulation assay. HEK-293 or LMTK- cells stably expressing human NPY receptor subtypes were stimulated with forskolin to elevate intracellular cAMP levels. NPY was added to inhibit forskolin-stimulated cAMP production. Test compounds were co-incubated to evaluate their ability to antagonize NPY-induced inhibition. After incubation, cells were lysed, and cAMP levels were quantified using a radioimmunoassay. [1] Radioligand binding assays were performed using membranes prepared from COS-7 cells that had been transiently transfected with cDNA encoding human NPY receptor subtypes (Y1, Y2, Y4, Y5). The assays utilized ¹²⁵I-labeled peptide YY (PYY) as the radioligand. Various concentrations of test compounds were incubated with the membrane preparations and radioligand to generate competition binding curves. Ki values were calculated from these curves to determine binding affinity. [1] Functional antagonist activity was assessed using a cAMP accumulation assay. HEK-293 or LMTK- cells stably expressing human NPY receptor subtypes were stimulated with forskolin to elevate intracellular cAMP levels. NPY was added to inhibit forskolin-stimulated cAMP production. Test compounds were co-incubated to evaluate their ability to antagonize NPY-induced inhibition. After incubation, cells were lysed, and cAMP levels were quantified using a radioimmunoassay. [1] |
| Cell Assay |
The cell-based functional assays employed stable cell lines (HEK-293 or LMTK-) expressing individual human NPY receptor subtypes. Cells were seeded in appropriate plates and allowed to adhere. For the assay, cells were treated with a combination of forskolin (to stimulate adenylate cyclase) and NPY (to activate the receptor and inhibit cAMP production), in the presence or absence of the test compound. After a defined incubation period, the reaction was stopped, and cell lysates were prepared. The concentration of cAMP in the lysates was measured using a specific radioimmunoassay kit. The ability of the test compound to reverse NPY-mediated inhibition of cAMP accumulation was used to determine its functional antagonistic potency (Kb). [1]
The cell-based functional assays employed stable cell lines (HEK-293 or LMTK-) expressing individual human NPY receptor subtypes. Cells were seeded in appropriate plates and allowed to adhere. For the assay, cells were treated with a combination of forskolin (to stimulate adenylate cyclase) and NPY (to activate the receptor and inhibit cAMP production), in the presence or absence of the test compound. After a defined incubation period, the reaction was stopped, and cell lysates were prepared. The concentration of cAMP in the lysates was measured using a specific radioimmunoassay kit. The ability of the test compound to reverse NPY-mediated inhibition of cAMP accumulation was used to determine its functional antagonistic potency (Kb). [1] |
| References | |
| Additional Infomation |
NTNCB hydrochloride is a class of highly potent and selective sulfonamide NPY Y5 receptor antagonists. Their discovery stemmed from the optimization of the weak, non-selective ligand phenethylamine. [1]
The introduction of the sulfonamide group is key to achieving high selectivity of the Y5 receptor relative to other NPY subtypes. [1] A combined model based on homology modeling and site-directed mutagenesis data shows that these antagonists interact with the Y5 receptor through key residues: sulfonamide NH forms a hydrogen bond with His398 in transmembrane helix 6 (TM6), the basic amine forms an ion pair with Glu211, and the two aromatic groups interact with the hydrophobic pocket in the receptor. This model explains their high efficiency and subtype selectivity. [1] These compounds have been confirmed as purely competitive antagonists in functional assays and are an important pharmacological tool for studying the physiological effects of the NPY Y5 receptor. [1] NTNCB hydrochloride is a class of highly potent and selective sulfonamide NPY Y5 receptor antagonists. Their discovery stemmed from the optimization of the weak, non-selective ligand phenethylamine. [1] The introduction of sulfonamide groups is key to achieving high selectivity for the Y5 receptor relative to other NPY subtypes. [1] The binding model, based on homology modeling and site-directed mutagenesis data, suggests that these antagonists interact with the Y5 receptor through key residues: sulfonamide NH forms a hydrogen bond with His398 in transmembrane helix 6 (TM6), the basic amine forms an ion pair with Glu211, and the two aromatic groups interact with the hydrophobic pocket in the receptor. This model explains their high efficiency and subtype selectivity. [1] Functional assays show that these compounds are purely competitive antagonists and are valuable pharmacological tools for studying the physiological function of the NPY Y5 receptor. [1] |
| Molecular Formula |
C25H34CLN3O4S
|
|---|---|
| Molecular Weight |
508.07
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| Exact Mass |
507.195
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| Elemental Analysis |
C, 59.10; H, 6.75; Cl, 6.98; N, 8.27; O, 12.60; S, 6.31
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| CAS # |
191931-56-3
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| Related CAS # |
486453-65-0; 191931-56-3 (HCl)
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| PubChem CID |
16759158
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
727
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.O=[N+](C1=CC=CC=C1S(NCC1CCC(CNC[C@H]2CCC3=CC=CC=C3C2)CC1)(=O)=O)[O-]
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| InChi Key |
BKCQHNDMUNWNQC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H33N3O4S.ClH/c29-28(30)24-7-3-4-8-25(24)33(31,32)27-18-20-11-9-19(10-12-20)16-26-17-21-13-14-22-5-1-2-6-23(22)15-21;/h1-8,19-21,26-27H,9-18H2;1H
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| Chemical Name |
2-nitro-N-[[4-[(1,2,3,4-tetrahydronaphthalen-2-ylmethylamino)methyl]cyclohexyl]methyl]benzenesulfonamide;hydrochloride
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| Synonyms |
NTNCB hydrochloride; NTNCB HCl
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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) |
DMSO: ~125 mg/mL (~246.0 mM)
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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 | 1.9682 mL | 9.8412 mL | 19.6823 mL | |
| 5 mM | 0.3936 mL | 1.9682 mL | 3.9365 mL | |
| 10 mM | 0.1968 mL | 0.9841 mL | 1.9682 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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