| Targets |
Nonapeptide-1 targets the melanocortin 1 receptor (MC1R) on melanocytes. It is a competitive antagonist of α-MSH at the MC1R, blocking the binding of α-MSH and preventing receptor activation. Nonapeptide-1 has a Ki of 40 nM for MC1R and is more selective for MC1R than for MC3R, MC4R, and MC5R (Ki values of 0.47, 1.34, and 2.4 μM, respectively) in COS-1 cells expressing human receptors. By blocking MC1R signaling, nonapeptide-1 inhibits melanin synthesis and reduces skin pigmentation.
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| ln Vitro |
Alpha-melanocyte hormone (α-MSH)-induced melanosome dispersion is inhibited by nonapeptide-1 (153N-6), with an IC50 value of 11 nM [1]. With an IC50 of 2.5 nM, nonapeptide-1 (0.1 nM-1 μM, 30 minutes) suppresses the intracellular cAMP levels in melanocytes that are produced by α-MSH [1]. Nonapeptide-1 (153N-6) was found to have the highest affinity (Ki: 40 nM) and to be more selective for MC1R than MC3R, MC4R, and MC5R (Ki: 0.47, 1.34, and 2.4 μM), respectively, in COS-1 cells that expressed human receptors [2]. In human epidermal melanocytes (HEM cells) and HaCaT cells, nonapeptide-1 (N-1A, 20 μM, 3 days) reverses UVA-induced melanin growth and suppresses basal melanin synthesis [3]. By binding to MC1R in HaCaT and HEM cells, nonapeptide-1 (20 μM, 3 days) competes with α-MSH to downregulate the expression of MC1R, tyrosinase, TRP1, TRP2, and MITF [3].
In vitro, nonapeptide-1 is a competitive α-MSH antagonist that potently inhibits α-MSH-induced intracellular cAMP accumulation in melanocytes with an IC₅₀ of 2.5 nM. It inhibits α-MSH-induced melanosome dispersion with an IC₅₀ of 11 nM. The peptide has a Ki of 40 nM for MC1R and is more selective for MC1R than for MC3R, MC4R, and MC5R (Ki values of 0.47, 1.34, and 2.4 μM, respectively). Nonapeptide-1 inhibits melanin synthesis in cell-based assays. These activities make it a valuable tool for studying skin pigmentation and related disorders. |
| ln Vivo |
In vivo, nonapeptide-1 has been studied for its effects on skin pigmentation. As a competitive antagonist of α-MSH at the MC1R, it inhibits melanin synthesis and reduces skin pigmentation. The peptide is used as an additive in skin-lightening and spot-corrective products. It has been studied for its potential in the regulation of steroid production in the adrenal gland and in skin cancer research. Comprehensive in vivo studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles.
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| Enzyme Assay |
In vitro receptor binding assays for nonapeptide-1 involve measuring its binding affinity to the melanocortin 1 receptor (MC1R). The receptor is incubated with a radiolabeled ligand and varying concentrations of nonapeptide-1. The displacement of the radiolabeled ligand is measured, and the Ki value is calculated. The compound's selectivity for MC1R over MC3R, MC4R, and MC5R is assessed using similar assays with each receptor subtype. These assays confirm the compound's mechanism of action as a selective MC1R antagonist.
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| Cell Assay |
Western Blot Analysis [3]
Cell Types: HaCaT cells, human epidermal melanocytes (HEM) Tested Concentrations: 20 μM Incubation Duration: 3 days Experimental Results: Down-regulated the expression of MC1R, tyrosinase, TRP1, TRP2 and MITF. In vitro cell-based assays for nonapeptide-1 evaluate its effects on melanocyte function. Melanocytes are cultured and treated with nonapeptide-1 in the presence or absence of α-MSH. Intracellular cAMP levels are measured using ELISA or radioimmunoassay. Melanosome dispersion is assessed by microscopy. Melanin synthesis is quantified by measuring melanin content or by using radioactive precursors. These assays confirm the compound's functional activity as an MC1R antagonist. |
| Animal Protocol |
In vivo animal experiments for nonapeptide-1 have not been extensively reported. For potential in vivo studies, nonapeptide-1 can be administered topically or via injection in animal models of hyperpigmentation. The compound's effects on skin pigmentation would be assessed by measuring melanin content in skin biopsies. Pharmacokinetic studies would determine the compound's absorption, distribution, metabolism, and excretion. Comprehensive in vivo studies are needed.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for nonapeptide-1 are limited. The peptide has a molecular weight of 1206.52 g/mol and is a synthetic peptide. As a peptide, it is expected to have poor oral bioavailability and is typically administered topically or via injection. The compound's stability in biological fluids and its potential for proteolytic degradation are important considerations for its use. Comprehensive ADME studies are needed.
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| Toxicity/Toxicokinetics |
The toxicity profile of nonapeptide-1 has not been extensively characterized. The peptide is for research use only and is not intended for human or veterinary use. In laboratory settings, nonapeptide-1 should be handled with appropriate safety precautions. Comprehensive toxicological studies are needed to fully characterize the safety profile of nonapeptide-1.
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| References |
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| Additional Infomation |
Nonapeptide-1 (Melanostatine-5) is a synthetic peptide that functions as a selective antagonist of the melanocortin 1 receptor (MC1R). It has a molecular formula of C₆₁H₈₇N₁₅O₉S and a molecular weight of 1206.52 g/mol. Nonapeptide-1 is a competitive α-MSH antagonist that inhibits α-MSH-induced intracellular cAMP and melanosome dispersion. It inhibits melanin synthesis and is used in skin-lightening products. The peptide is for research use only.
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| Exact Mass |
1205.653
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|---|---|
| CAS # |
158563-45-2
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| Related CAS # |
Nonapeptide-1 acetate salt
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| PubChem CID |
10418849
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.672
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
12
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
33
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| Heavy Atom Count |
86
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| Complexity |
2280
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| Defined Atom Stereocenter Count |
9
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| InChi Key |
KNFLNGRLKALWRF-LDXSYGEZSA-N
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| InChi Code |
InChI=1S/C61H87N15O9S/c1-37(2)51(52(64)77)74-58(83)50-26-16-31-76(50)60(85)45(23-12-13-28-62)70-55(80)46(33-38-17-6-4-7-18-38)71-56(81)48(35-40-36-68-43-22-11-10-21-41(40)43)72-53(78)44(24-14-29-67-61(65)66)69-54(79)47(34-39-19-8-5-9-20-39)73-57(82)49-25-15-30-75(49)59(84)42(63)27-32-86-3/h4-11,17-22,36-37,42,44-51,68H,12-16,23-35,62-63H2,1-3H3,(H2,64,77)(H,69,79)(H,70,80)(H,71,81)(H,72,78)(H,73,82)(H,74,83)(H4,65,66,67)/t42-,44-,45-,46-,47+,48+,49-,50-,51-/m0/s1
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| Chemical Name |
(2S)-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-1-[(2S)-2-amino-4-methylsulfanylbutanoyl]pyrrolidine-2-carboxamide
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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