| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MC1R MC3R 0.47 μM (Ki) MC4R 1.34 μM (Ki) MC5R 2.4 μM (Ki)
Nonapeptide-1 acetate salt specifically and selectively targets the melanocortin 1 receptor (MC1R), a G-protein-coupled receptor (GPCR) primarily expressed on the surface of melanocytes. Upon binding to MC1R, it competitively blocks the binding of the endogenous agonist alpha-melanocyte-stimulating hormone (alpha-MSH). This antagonism prevents the activation of the receptor and the subsequent coupling to Gs protein. As a result, it inhibits the downstream activation of adenylyl cyclase and the production of the second messenger cyclic AMP (cAMP). The reduction in cAMP levels leads to decreased activity of protein kinase A (PKA), which is a key driver of melanogenesis. Consequently, the expression of microphthalmia-associated transcription factor (MITF) is downregulated, leading to reduced transcription of key melanogenic enzymes such as tyrosinase, TRP1, and TRP2, ultimately suppressing melanin synthesis and melanosome transport. |
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| ln Vitro |
Nonapeptide-1 acetate salt(153N-6) has an IC50 value of 11 nM and inhibits the dispersion of melanosomes caused by α-melanocyte hormone (α-MSH). Melanocytes exposed to α-MSH-induced intracellular cAMP levels are inhibited by nonapeptide-1 acetate salt (0.1 nM-1 μM, 30 min), with an IC50 of 2.5 nM[1]. Nonapeptide-1 acetate salt (153N-6) is preferential for MC1R over MC3R, MC4R, and MC5R (Ki: 0.47, 1.34, and 2.4 μM, respectively) and has the highest affinity for MC1R (Ki: 40 nM) in COS-1 cells expressing human receptors[2]. Human epidermal melanocytes (HEM cells) and HaCaT cells are treated with nonapeptide-1 acetate salt (N-1A, 20 μM, 3 days) to decrease basal melanin synthesis and reverse UVA-induced melanin increase[3]. Nonapeptide-1 acetate salt (20 μM, 3 days) binds to MC1R in HaCaT and HEM cells, competing with α-MSH to downregulate the expression of MC1R, tyrosinase, TRP1, TRP2, and MITF[3].
In vitro studies have shown that Nonapeptide-1 acetate salt is a highly potent alpha-MSH antagonist. In melanocyte cultures, it inhibits alpha-MSH-induced intracellular cAMP levels with an IC50 of 2.5 nM and alpha-MSH-induced melanosome dispersion with an IC50 of 11 nM. It demonstrates selectivity for MC1R over other melanocortin receptors, with Ki values of 0.47 uM for MC3R, 1.34 uM for MC4R, and 2.4 uM for MC5R. Furthermore, in Human Epidermal Melanocytes (HEM) and HaCaT cells, Nonapeptide-1 acetate salt (20 uM, 3 days) inhibits basal melanin synthesis and reverses UVA-induced melanin increase. It also downregulates the expression of MC1R, tyrosinase, TRP1, TRP2, and MITF. The compound has a molecular weight of 1266.56 g/mol and a formula of C63H91N15O11S. |
| ln Vivo |
While the specific in vivo activity of this exact acetate salt is not detailed, the biological effects are inferred from its in vitro mechanism of action and the known pharmacology of MC1R. In animal models, such as topical or intradermal application in pigmentation models (e.g., C57BL/6 mice injected with alpha-MSH), it is expected to induce skin lightening by competitively antagonizing the effects of alpha-MSH. It could also be utilized in models of adrenal function to study the role of MC2R or in models of skin cancer, given that MC1R is known to have a protective role against UV-induced DNA damage. The specific acetate salt form is primarily used as a chemical probe for these pathway studies.
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| Enzyme Assay |
Cell-free receptor binding assays are used to determine the selectivity and affinity (Ki) of Nonapeptide-1 acetate salt for MC1R. The standard protocol involves using COS-1 cells that are transiently transfected with and express high levels of human MC1R receptors. A membrane fraction is prepared from these cells. For the competition binding assay, the membranes (10-20 ug/well) are incubated with a trace amount (e.g., 0.05-0.1 nM) of a radiolabeled tracer, such as [125I]-NDP-alpha-MSH, a high-affinity alpha-MSH analog. Various concentrations of unlabeled Nonapeptide-1 acetate salt (from 1 pM to 100 uM) are added to compete with the tracer. The reaction is carried out in a 96-well filter plate for 60-90 minutes at 25degC. The bound and free radioligand are then separated by rapid filtration through GF/B glass fiber filters using a cell harvester. The filters are washed several times with cold assay buffer to remove unbound radioligand. The retained radioactivity on the dried filters is measured using a gamma counter or liquid scintillation counter. The Ki value (40 nM) is calculated from the IC50 of the competition curve using the Cheng-Prusoff equation.
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| Cell Assay |
Western Blot Analysis[3]
Cell Types: HaCaT cells, Human epidermal melanocytes(HEM) Tested Concentrations: 20 μΜ Incubation Duration: 3 days Experimental Results: Downregulated the expression of MC1R, tyrosinase, TRP1, TRP2, and MITF. A typical cell-based assay involves treating melanocytes or melanoma cell lines (such as B16-F10 mouse melanoma or human HEM cells) to evaluate the functional antagonism of the alpha-MSH receptor. The following protocol is commonly used for a cAMP inhibition assay: cells are seeded in 96-well plates and allowed to reach confluence. They are then serum-starved for 2-4 hours. The cells are pre-incubated with serial dilutions of Nonapeptide-1 acetate salt (0.01 nM to 10 uM) for 30 minutes. Subsequently, the cells are stimulated with a sub-maximal concentration of alpha-MSH (e.g., 10-100 nM) or an MC1R-specific agonist like NDP-alpha-MSH for an additional 30-60 minutes. After stimulation, the cells are lysed, and the intracellular cAMP levels are measured using a competitive ELISA or a homogeneous time-resolved fluorescence (HTRF) cAMP detection kit. The inhibition curve is plotted, and the IC50 value (2.5 nM for cAMP inhibition) is determined. |
| Animal Protocol |
While no specific in vivo protocol for the acetate salt is published, a general protocol for studying skin pigmentation can be used as a reference. To assess the depigmenting effect, the dorsal skin of 4-6 week old C57BL/6 mice is shaved. Mice are divided into treatment groups (n=5-10 per group). The peptide (Nonapeptide-1 acetate salt) is dissolved in a suitable vehicle (e.g., phosphate-buffered saline, pH 7.4, or a water-based cream). The test agent is applied topically to the shaved skin area at a dose of, for example, 0.5-2 mg/cm2, once daily for 4-6 weeks. The alpha-MSH group (positive control) receives daily intradermal injections of alpha-MSH (0.5-1 mg/kg). At the end of the treatment, skin samples are collected. Melanin content is determined by spectrophotometry after dissolving skin biopsies in 1N NaOH. Also, visual observation of skin color and histological analysis of skin sections (Fonatana-Masson staining for melanin and immunohistochemistry for melanogenic proteins) are performed to evaluate the depigmenting efficacy.
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| ADME/Pharmacokinetics |
This compound is provided as a stable, lyophilized acetate salt. The powder should be stored in a sealed container at -20degC, protected from moisture and light, where it is stable for up to 3 years. For in vitro use, a stock solution is typically prepared by dissolving the powder in sterile water or DMSO to a concentration of 1-10 mM. This stock solution can be stored at -80degC for up to 6 months and at -20degC for up to 1 month, avoiding repeated freeze-thaw cycles. For in vivo formulation, it can be dissolved in saline or PBS, or diluted in a formulation of DMSO:PEG300:Tween80:Saline (e.g., 10:40:5:45) to achieve a clear solution. The molecular weight is 1266.56 g/mol, and it is freely soluble in water, PBS, and DMSO.
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| Toxicity/Toxicokinetics |
This product is intended for research use only and is not approved for clinical or therapeutic applications. No direct toxicity has been reported for this compound at concentrations used in standard research settings. However, as with all peptides, the acetate counterion is generally considered non-toxic in research quantities. Standard laboratory safety practices, including the use of PPE, should be followed to avoid inhalation, ingestion, or skin contact. The primary caution is that it may inhibit the MC1R pathway, which is part of the skin‘s natural defense mechanism against UV-induced DNA damage, potentially increasing UV sensitivity in treated areas.
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| References |
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| Additional Infomation |
Nonapeptide-1 acetate salt is a well-established research tool for studying melanogenesis and MC1R signaling pathways. It is a competitive antagonist of alpha-MSH with a molecular weight of 1266.56 g/mol and formula C63H91N15O11S. The compound is particularly useful for developing and testing depigmenting agents for skin hyperpigmentation disorders such as melasma and solar lentigo. It can also be used to study the role of MC1R in adrenal steroidogenesis and skin cancer, including melanoma. It is not a drug and is not intended for human use. The free base CAS number for the compound is 158563-45-2.
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| Molecular Formula |
C63H91N15O11S
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| Molecular Weight |
1266.56
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| Related CAS # |
Nonapeptide-1;158563-45-2
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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) |
H2O :~50 mg/mL (~39.48 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (39.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7895 mL | 3.9477 mL | 7.8954 mL | |
| 5 mM | 0.1579 mL | 0.7895 mL | 1.5791 mL | |
| 10 mM | 0.0790 mL | 0.3948 mL | 0.7895 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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