![[S5K, F6Y, L9mL, M10Mox] neurokinin A (4–10)](/upload/0319/V118439.png)
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| Targets |
[S5K, F6Y, L9mL, M10Mox] neurokinin A (4-10) targets the neurokinin-1 receptor (NK1R), a G protein-coupled receptor (GPCR) of the tachykinin receptor family. While its parent neurokinin A has higher affinity for NK2R, this analog is specifically modified to exhibit high selectivity for NK1R over NK2R and NK3R. The modifications at positions L9mL (N-methyl-leucine) and M10Mox (O-methyl-homoserine) increase resistance to proteolytic degradation, extending its in vivo half-life to 10.3 hours in mice. Upon binding to NK1R, the peptide acts as an agonist, activating Gq/11 protein signaling, increasing intracellular calcium, and inducing downstream effects such as vasodilation, plasma extravasation, smooth muscle contraction, and pain transmission. It operates within the tachykinin and neuropeptide signaling pathways. [14L12-L17]
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| ln Vitro |
In vitro, [S5K, F6Y, L9mL, M10Mox] neurokinin A (4-10) acts as a selective NK1R agonist. Its activity is typically measured in cell-based calcium mobilization assays using CHO-K1 cells stably expressing human NK1R. The peptide induces concentration-dependent increases in intracellular calcium with an EC50 in the low nanomolar to sub-nanomolar range (specific value not publicly detailed). It exhibits high selectivity for NK1R over NK2R and NK3R, as shown by lack of significant activity in cells expressing those receptor subtypes. The peptide also induces NK1R internalization and downstream signaling (e.g., ERK1/2 phosphorylation). No cytotoxicity is observed at effective concentrations. DMSO is used as solvent for stock solutions (≤0.1% in assays). Positive control: substance P (full-length NK1R agonist). Negative control: vehicle (PBS). [14L12-L14]
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| ln Vivo |
In vivo, [S5K, F6Y, L9mL, M10Mox] neurokinin A (4-10) has an extended half-life of 10.3 hours in mice, significantly longer than native neurokinin A. This prolonged duration is achieved through modifications (N-methyl-leucine at position 9 and O-methyl-homoserine at position 10) that confer resistance to proteolytic degradation. The compound is expected to produce sustained NK1R-mediated effects such as neurogenic inflammation (plasma extravasation), pain behaviors, and smooth muscle contraction. Specific dosing and efficacy data are not detailed in public sources. For research use only. [14L13-L14]
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| Enzyme Assay |
For non-cellular NK1R binding assays, prepare membranes from CHO-K1 cells stably expressing human NK1R. Incubate membranes (10-20 microg) with 0.1 nM [3H]substance P and varying concentrations of the compound (0.001-1000 nM, 10-point 3-fold dilutions) in 50 mM Tris-HCl pH 7.4, 5 mM MnCl2, 0.1% BSA, 40 microg/mL bacitracin, 4 microg/mL chymostatin in 96-well plates for 60-90 min at 25degC. Terminate reaction by filtration through GF/B filters presoaked in 0.3% PEI. Wash 3× with ice-cold buffer. Count filters on gamma or scintillation counter. Non-specific binding determined with 1 microM unlabeled substance P. Calculate IC50 and Ki (Cheng-Prusoff equation). Positive control: substance P (Ki ~0.5-1 nM). Negative control: DMSO only (≤1%). [14L12-L14]
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| Cell Assay |
For in vitro cell-based calcium mobilization assay, culture CHO-K1 cells stably expressing human NK1R in Ham's F-12 medium with 10% FBS at 37degC, 5% CO2. Seed cells in black 96-well plates (2×10⁴ cells/well) and culture overnight. Load cells with Fluo-4 AM (5 microM) in HBSS with 0.02% Pluronic F-127 and 2.5 mM probenecid for 30-45 min at 37degC. Wash twice with HBSS. Add the compound (0.001-1000 nM, prepared in PBS with 0.1% BSA, final DMSO ≤0.1%) and measure fluorescence (Ex 488 nm/Em 535 nm) for 60-90 s using a plate reader. Calculate EC50 from dose-response curve. For selectivity, repeat in cells expressing NK2R or NK3R. Positive control: substance P (EC50 ~0.5-2 nM for NK1R). Negative control: vehicle. All experiments in triplicate. [14L12-L14]
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| Animal Protocol |
For in vivo pharmacokinetic and pharmacodynamic studies, male C57BL/6 mice (6-8 weeks, 20-25 g, n=5/time point) are used. The compound is formulated in sterile PBS or 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline to a concentration of 0.5-2 mg/mL. Administer intravenously (IV) via tail vein at a dose of 0.1-1 mg/kg. For plasma half-life determination, collect blood samples at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 h post-dose, centrifuge, and analyze plasma by LC-MS/MS to quantify peptide concentration. Terminal half-life (t½) is reported as 10.3 hours. For pharmacodynamic studies (e.g., plasma extravasation), inject Evans blue dye (2% in saline, 2 mL/kg) intravenously, then administer the compound intradermally or intravenously, and quantify extravasation by spectrophotometry of skin punch biopsies. For research use only. [14L13-L14]
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| References | |
| Additional Infomation |
[S5K, F6Y, L9mL, M10Mox] neurokinin A (4-10) has a molecular weight of 821.96 and a molecular formula of C38H63N9O11. The compound is a synthetic peptide with the sequence Asp-Lys-Tyr-Val-Gly-{Leu(Me)}-{Hse(Me)}-NH2 (DKYVG-{Leu(Me)}-{Hse(Me)}-NH2). It has a prolonged in vivo half-life of 10.3 hours in mice due to N-methyl-leucine and O-methyl-homoserine modifications that confer proteolytic resistance. Solubility: DMSO (~50 mg/mL). Storage: powder at -20degC for 3 years; in DMSO at -80degC for 6 months. Shipping: ambient temperature. For research use only-not for human use. [14L15-L20][34L15-L22]
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| Molecular Formula |
C38H63N9O11
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| Molecular Weight |
821.96
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| CAS # |
2770688-17-8
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| Sequence |
Asp-Lys-Tyr-Val-Gly-{Leu(Me)}-{Hse(Me)}-NH2DKYVG-{Leu(Me)}-{Hse(Me)}-NH2
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| Appearance |
White to off-white solid powder
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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 : ~50 mg/mL (~60.83 mM; with sonication)
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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 | 1.2166 mL | 6.0830 mL | 12.1660 mL | |
| 5 mM | 0.2433 mL | 1.2166 mL | 2.4332 mL | |
| 10 mM | 0.1217 mL | 0.6083 mL | 1.2166 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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