| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
The primary target of NS3861 is the nicotinic acetylcholine receptor (nAChR), specifically the α3β2 and α3β4 subtypes. It acts as a full agonist at α3β2 nAChRs and a partial agonist at α3β4 nAChRs. The compound has a binding Ki of 0.62 nM at α3β4 nAChRs and EC50 values of 1.6 μM at α3β2 receptors and 1 μM at α3β4 receptors. NS3861 exhibits minimal activity at α4β2 and α4β4 nAChRs. By binding to and activating these receptors, NS3861 modulates neurotransmitter release and neuronal excitability. The compound's high affinity for α3β4 nAChRs and its partial agonist activity make it a valuable tool for studying the role of these receptors in pain, addiction, and autonomic function.
|
|---|---|
| ln Vitro |
In the HEK293 cell line, NS3861 fumarate shows an opposite preference for β-subunit and completely lacks activation of α4-containing receptors. Fumarate NS3861 selectively activates nAChRs that include α3, but not α4 nAChRs. It has greater efficiency at α3β2 receptors than at α3β4 receptors. For the α3β2 and α3β4 receptors, the EC50 values are 1.7 and 0.15 μM, respectively[1]. High affinity and partial agonist characteristics are shown by NS3861 fumarate at α3β4-expressing nAChR [2].
In vitro, NS3861 is a novel and potent α3β2 nAChR full agonist and α3β4 partial agonist. It has a binding Ki of 0.62 nM at α3β4 nAChRs and EC50 values of 1.6 μM at α3β2 receptors and 1 μM at α3β4 receptors. NS3861 exhibits minimal activity at α4β2 and α4β4 nAChRs. The compound's activity is typically measured using radioligand binding assays with cell membranes expressing nAChRs of various subunit compositions, and functional assays using electrophysiological recordings or calcium imaging in cells expressing these receptors. These assays confirm that NS3861 is a potent and efficacious agonist at α3-containing nAChRs. |
| ln Vivo |
In vivo, NS3861 can enhance fecal pellet expulsion in a dose-dependent manner in mice that received long-term, but not short-term, morphine treatment. This suggests that NS3861 may modulate gastrointestinal motility through its action on nAChRs, and that this effect is dependent on the duration of morphine exposure. The compound's ability to modulate nAChR activity in vivo makes it a valuable tool for studying the role of these receptors in various physiological and pathological processes, including pain, addiction, and gastrointestinal function.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NS3861 involve radioligand binding studies using cell membranes expressing nAChRs of various subunit compositions. Competitive binding assays are performed using a radiolabeled nAChR ligand (e.g., [3H]epibatidine) to determine the compound's affinity (Ki) for the receptor. Selectivity profiling against other nAChR subtypes (α4β2, α4β4) and other neurotransmitter receptors is performed to assess the compound's specificity. Functional assays using electrophysiological recordings (e.g., patch-clamp, two-electrode voltage clamp) or calcium imaging in cells expressing nAChRs are employed to assess the compound's ability to activate the receptor and to determine its efficacy as a full or partial agonist.
|
| Cell Assay |
In vitro cellular assays for NS3861 are conducted in cell lines expressing nAChRs of various subunit compositions. Cells are treated with varying concentrations of NS3861, and receptor activation is assessed using calcium imaging, fluorescent membrane potential dyes, or electrophysiological recordings. The compound's full agonist activity at α3β2 receptors and partial agonist activity at α3β4 receptors are confirmed by measuring its maximal effect relative to a full agonist such as acetylcholine. These assays confirm that NS3861 engages its target in a cellular context and produces the expected activation of nAChRs.
|
| Animal Protocol |
In vivo animal studies for NS3861 have been conducted in mice to assess its effects on gastrointestinal motility. Mice that received long-term morphine treatment were administered NS3861, and fecal pellet expulsion was measured as a readout of gastrointestinal motility. The compound enhanced fecal pellet expulsion in a dose-dependent manner in long-term morphine-treated mice but not in short-term morphine-treated mice. This suggests that NS3861 may modulate gastrointestinal motility through its action on nAChRs, and that this effect is dependent on the duration of morphine exposure. Additional studies could be performed in animal models of pain and addiction to assess the compound's therapeutic potential.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NS3861 indicate that it has a molecular weight of 416.30 and is typically available as the fumarate salt. The compound is soluble in DMSO, facilitating its use in in vitro assays and formulation for in vivo administration. For storage, the powder should be kept under appropriate conditions to maintain stability. The compound's purity is typically high, ensuring quality and reproducibility in experimental studies.
|
| Toxicity/Toxicokinetics |
The toxicological profile of NS3861 is primarily derived from its use as a research compound in preclinical studies. As a nAChR agonist, potential on-target effects could include changes in autonomic function, pain perception, and addiction-related behaviors, given the roles of α3-containing nAChRs in these processes. The compound's partial agonist activity at α3β4 receptors may reduce the risk of desensitization and tolerance compared to full agonists. Comprehensive toxicology studies would be required for therapeutic development, including assessments of neurological, cardiovascular, and gastrointestinal function.
|
| References | |
| Additional Infomation |
NS3861 is a novel and potent α3β2 nAChR full agonist and α3β4 partial agonist. It has a binding Ki of 0.62 nM at α3β4 nAChRs and EC50 values of 1.6 μM at α3β2 receptors and 1 μM at α3β4 receptors. NS3861 exhibits minimal activity at α4β2 and α4β4 nAChRs. The compound can enhance fecal pellet expulsion in a dose-dependent manner in mice that received long-term morphine treatment. NS3861 is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
|
| Molecular Formula |
C16H18BRNO4S
|
|---|---|
| Molecular Weight |
400.28
|
| Exact Mass |
399.013
|
| CAS # |
216853-60-0
|
| Related CAS # |
NS3861;216853-59-7
|
| PubChem CID |
91826078
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
23
|
| Complexity |
410
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C2CCC1C=C(C2)C3=C(C=CS3)Br.C(=C/C(=O)O)\C(=O)O
|
| InChi Key |
KXBSQPLWTVQFGJ-WLHGVMLRSA-N
|
| InChi Code |
InChI=1S/C12H14BrNS.C4H4O4/c1-14-9-2-3-10(14)7-8(6-9)12-11(13)4-5-15-12;5-3(6)1-2-4(7)8/h4-6,9-10H,2-3,7H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1+
|
| Chemical Name |
3-(3-bromothiophen-2-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene;(E)-but-2-enedioic acid
|
| Synonyms |
NS 3861 NS-3861 NS3861
|
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~249.82 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.25 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 (6.25 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4983 mL | 12.4913 mL | 24.9825 mL | |
| 5 mM | 0.4997 mL | 2.4983 mL | 4.9965 mL | |
| 10 mM | 0.2498 mL | 1.2491 mL | 2.4983 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
