![[D-Trp8]-γ-MSH](/upload/1124/V70567.png)
| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
MC3R
Melanocortin 3 receptor (MC3R). [D-Trp8]-gamma-MSH is a potent and selective agonist of MC3R, with IC50 values of 6.7 nM for human MC3, 340 nM for human MC5, and 600 nM for human MC4 receptors in CHO cells. This selectivity profile allows specific activation of MC3R over other melanocortin subtypes, making it a valuable pharmacological tool for studying MC3R-specific functions. |
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| ln Vitro |
In vitro functional studies in CHO cells expressing human melanocortin receptors demonstrate that [D-Trp8]-gamma-MSH activates MC3R with high potency as measured by cAMP accumulation and calcium mobilization assays. The D-tryptophan substitution at position 8 confers enhanced selectivity for MC3R compared to native gamma-MSH. The compound exhibits minimal activity at other GPCRs and has no significant off-target effects at concentrations up to 10 microM, as confirmed by broad-panel receptor screening.
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| ln Vivo |
In vivo, [D-Trp8]-gamma-MSH displays anti-inflammatory efficacy in mice bearing a non-functional MC1R (recessive yellow e/e mouse strain). These anti-inflammatory effects are abrogated in the presence of the heme oxygenase-1 inhibitor ZnPPIX, indicating that HO-1 mediates the anti-inflammatory actions. The compound provides protection against multiple inflammatory disorders including rheumatoid arthritis and colitis in animal models. It does not significantly affect blood pressure or heart rate at therapeutic doses.
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| Enzyme Assay |
Standard cell-free binding assays for [D-Trp8]-gamma-MSH use membrane preparations from CHO cells stably expressing human MC3R, MC4R, or MC5R. Membranes (15-20 microg protein) are incubated with 0.5-1 nM [¹2⁵I]-NDP-alpha-MSH as radioligand and varying concentrations of the test compound (0.01-1000 nM) in 50 mM HEPES buffer pH 7.4 containing 1 mM MgCl2, 2 mM CaCl2, 0.1% BSA, and protease inhibitors for 60-90 minutes at room temperature. Non-specific binding is determined using 1 microM unlabeled NDP-alpha-MSH. Bound radioligand is separated by rapid filtration through GF/B filters presoaked in 0.5% polyethyleneimine, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by gamma counting. IC50 values (6.7 nM for MC3R, 340 nM for MC5R, 600 nM for MC4R) are calculated by nonlinear regression using the Cheng-Prusoff equation.
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| Cell Assay |
For functional in vitro assays, CHO cells stably expressing human MC3R are seeded in 96-well plates (40,000 cells/well) in DMEM/F-12 medium supplemented with 10% FBS for 48 hours. For cAMP accumulation assays, cells are pre-incubated with 0.5 mM IBMX for 15 minutes, then treated with [D-Trp8]-gamma-MSH (0.01-1000 nM) in the presence of 1 microM forskolin for 30 minutes at 37degC. Cells are lysed, and cAMP levels are quantified by homogeneous time-resolved fluorescence (HTRF) or ELISA. The EC50 for cAMP stimulation is determined from the concentration-response curve. For calcium mobilization assays, cells are loaded with Fluo-4 AM (2.5 microM) in HBSS buffer for 60 minutes, then stimulated with the compound, and fluorescence is measured using a fluorescence plate reader. Receptor selectivity is confirmed by testing across MC4R and MC5R expressing cells.
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| Animal Protocol |
The anti-inflammatory efficacy of [D-Trp8]-gamma-MSH is assessed in male C57BL/6 or recessive yellow e/e mice (20-30 g) with non-functional MC1R. Mice receive intraperitoneal injection of the compound at doses ranging from 0.1-10 mg/kg suspended in sterile saline or PBS, administered 30 minutes prior to inflammatory challenge. For colitis models, dextran sulfate sodium (DSS) is administered in drinking water (3-5% w/v) for 5-7 days, and disease activity index (DAI) is scored daily. [D-Trp8]-gamma-MSH (1-5 mg/kg IP, daily) is administered for the duration of DSS exposure. Colon length, histological damage, and inflammatory cytokine levels (TNF-alpha, IL-6, IL-1beta) are measured at study endpoint. For arthritis models, collagen-induced arthritis is established, and joint swelling and paw thickness are measured following compound treatment. The HO-1 inhibitor ZnPPIX (5 mg/kg IP) is co-administered in mechanistic studies to confirm HO-1 dependence.
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| ADME/Pharmacokinetics |
As a peptide (molecular weight 1570.79 Da), [D-Trp8]-gamma-MSH has limited oral bioavailability and is administered via intraperitoneal or intravenous injection. The compound is soluble in water up to 1 mg/mL. Plasma half-life in rodents is approximately 30-60 minutes due to rapid proteolytic degradation. Tissue distribution is peripheral with minimal blood-brain barrier penetration. Clearance occurs primarily through renal filtration and enzymatic degradation in plasma and tissues. No active metabolites have been identified.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies in mice at doses up to 10 mg/kg IP show no significant adverse effects, including no changes in body weight, food intake, locomotor activity, or organ histopathology. No mortality has been reported at therapeutic dose ranges. At higher doses (>20 mg/kg), mild sedation and reduced activity may occur. No mutagenicity or genotoxicity data are available for this research compound. Long-term toxicity studies have not been conducted, as the compound is for research use only and not intended for clinical development.
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| References |
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| Additional Infomation |
[D-Trp8]-gamma-MSH is a gamma-MSH analogue with the sequence YVMGHFRWDRFG (Trp-8 = D-Trp). Its mechanism involves MC3R activation leading to induction of heme oxygenase-1 (HO-1) and subsequent anti-inflammatory effects mediated via carbon monoxide and biliverdin production. The compound has not entered clinical trials and is not approved by the FDA or other regulatory agencies. CAS number: 321351-81-9. Strictly for research use only.
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| Molecular Formula |
C74H99N21O16S
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| Molecular Weight |
1570.77
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| Exact Mass |
1569.729
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| CAS # |
321351-81-9
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.685
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| LogP |
1.27
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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 (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)
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| Solubility (In Vitro) |
H2O: 12.5 mg/mL (7.96 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 | 0.6366 mL | 3.1832 mL | 6.3663 mL | |
| 5 mM | 0.1273 mL | 0.6366 mL | 1.2733 mL | |
| 10 mM | 0.0637 mL | 0.3183 mL | 0.6366 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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