| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
Ki: 4.4 μM (NK-2 receptor, rat small intestine)[1]
Men 10376 specifically targets the neurokinin-2 (NK2) receptor, a G protein-coupled receptor (GPCR) that is activated by the endogenous peptide neurokinin A (NKA). It acts as a competitive antagonist, binding to the receptor and blocking the action of NKA. |
|---|---|
| ln Vitro |
Men 10376 exhibits low selectivity for NK-1 and NK-3 receptors (Ki, >10 μM) and is a selective tachykinin NK-2 receptor with a Ki of 4.4 μM[1]. Men 10376 exhibits pA2s for NK-1 (guinea-pig ileum) and NK-2 (endothelium-deprived rabbit pulmonary artery) receptors, respectively, of 5.66 and 8.08. The NK-3 receptor (Ki, >10 μM) is unaffected by Men 10376[2].
In isolated rabbit pulmonary artery, which is endogenously enriched in NK2 receptors, Men 10376 selectively inhibits NKA-induced contractions with a pA2 value of 8.08. It is selective for NK2 receptors in this tissue over NK2 receptors in other tissues (pA2=5.64 in hamster trachea). It has a Ki of 4.4 uM for the NK2 receptor in the rat small intestine and low affinity for NK1 and NK3 receptors (Ki >10 uM). |
| ln Vivo |
In rats, the NK-2 receptor agonist-induced increase in bladder motility is countered by Men 10376 (1 and 3 μmol/kg)[2].
Men 10376 inhibits NK2 receptor-mediated functions in vivo. In anesthetized rats, administration of Men 10376 (1 and 3 micromol/kg) antagonizes the increase in bladder motility induced by the NK2 receptor agonist [beta-Ala8]-NKA(4-10). It also inhibits [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in anesthetized guinea pigs. |
| Enzyme Assay |
A standard NK2 receptor binding assay uses membrane preparations from cells expressing the human NK2 receptor. The membranes are incubated with a high-affinity radioligand (e.g., [¹2⁵I]-Neurokinin A) and increasing concentrations of Men 10376 TFA. Non-specific binding is defined using an excess of unlabeled NKA. After incubation, bound radioligand is separated from free by filtration, and the radioactivity on the filters is counted to determine the Ki value.
|
| Cell Assay |
A standard in vitro functional assay involves measuring the contraction of isolated rabbit pulmonary artery rings, which is the classic assay for NK2 receptor activity. The artery rings are mounted in an organ bath system filled with oxygenated Krebs-Henseleit buffer. After an equilibration period, the tissue is pre-contracted with a submaximal concentration of an NK2 agonist like NKA or [beta-Ala8]-NKA(4-10). Then, Men 10376 is added to the bath in a cumulative manner to measure the relaxation response. The pA2 value is calculated as a measure of antagonist potency.
|
| Animal Protocol |
For in vivo experiments, Men 10376 is administered intravenously via a cannula to anesthetized rats, either as a bolus or by continuous infusion. After confirming stable bladder motility, the NK2 receptor agonist [beta-Ala8]-NKA(4-10) is administered intravenously to induce a standard contractile response. The ability of Men 10376 to block this response is measured.
|
| ADME/Pharmacokinetics |
As a peptide, Men 10376 TFA is soluble in water at 1.43 mg/mL (1.20 mM). It is typically supplied as a lyophilized powder and stored at -20degC, protected from light, to maintain stability. The TFA salt enhances its solubility and stability.
|
| Toxicity/Toxicokinetics |
The primary toxicological concern for a NK2 antagonist is the potential for unwanted side effects, such as constipation, due to its ability to block smooth muscle contraction in the gut. However, as a research tool, the compound is used at very low doses, and no specific toxicity data is provided.
|
| References | |
| Additional Infomation |
Men 10376 TFA is a research-grade, highly selective antagonist of the NK2 receptor. It is a valuable tool for dissecting the role of tachykinin signaling in various physiological processes, including visceral pain, inflammation, and asthma. It is not a drug and is not intended for human therapeutic use. This product is strictly for laboratory research.
|
| Molecular Formula |
C59H69F3N12O12
|
|---|---|
| Molecular Weight |
1195.25
|
| Related CAS # |
Men 10376;135306-85-3
|
| Appearance |
White to off-white solid powder
|
| 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) |
H2O :~1.43 mg/mL (~1.20 mM)
|
|---|---|
| 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 | 0.8366 mL | 4.1832 mL | 8.3665 mL | |
| 5 mM | 0.1673 mL | 0.8366 mL | 1.6733 mL | |
| 10 mM | 0.0837 mL | 0.4183 mL | 0.8366 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
