What is the difference between Melanotan I and Melanotan II?

Melanotan I, also known as afamelanotide, is a linear 13-amino-acid alpha-MSH analog ([Nle4, D-Phe7]-alpha-MSH) that is relatively MC1R-preferring and therefore acts mainly on pigmentation; it has been developed as an approved implant for erythropoietic protoporphyria. Melanotan II is a shorter, conformationally constrained cyclic heptapeptide that is more potent but far less selective, engaging MC1R, MC3R, MC4R and MC5R. This broader receptor coverage explains why MT-II produces effects beyond pigmentation, including MC4R-mediated changes in sexual arousal and appetite.

How does Melanotan II stimulate skin pigmentation?

Melanotan II activates MC1R on epidermal melanocytes. MC1R is Gs-coupled, so agonism stimulates adenylyl cyclase, raising cAMP and activating protein kinase A and the transcription factor CREB. This upregulates MITF, the master regulator of melanocyte biology, which in turn drives expression of tyrosinase, TRP-1 and TRP-2. The result is a shift of melanogenesis toward eumelanin, the dark brown-black pigment, producing skin darkening that is independent of ultraviolet exposure.

Why does Melanotan II affect sexual function and appetite?

These effects are mediated by central melanocortin receptors rather than MC1R. MC4R and MC3R are expressed in hypothalamic and other CNS regions. MC4R activation in the paraventricular nucleus suppresses food intake and increases energy expenditure, which is why MC4R is one of the most important genetic targets in monogenic obesity. Melanocortin signaling in spinal and hypothalamic circuits also modulates erectile and sexual arousal pathways, an observation that led to the development of the MC4R-selective analog bremelanotide from the same peptide lineage.

What is the significance of the lactam cyclization in Melanotan II?

Melanotan II is cyclized through an amide (lactam) bridge between the side-chain carboxyl of aspartic acid at position 2 and the epsilon-amino group of lysine at position 7. This covalent constraint locks the critical His-D-Phe-Arg-Trp pharmacophore into the bioactive beta-turn conformation, dramatically increasing receptor affinity and prolonging duration of action. Cyclization also protects the peptide backbone from exopeptidase and endopeptidase degradation, and the D-phenylalanine substitution further resists proteolysis.

How should Melanotan II peptide be reconstituted and stored?

The lyophilized powder should be stored sealed at -20C, protected from light and moisture, where it is stable long term. It is soluble in water, dilute acetic acid and DMSO; for stubborn dissolution a small volume of dilute acetic acid or ammonium hydroxide can be used before dilution into buffer. After reconstitution, aliquot into single-use low-binding vials, store at -20C or -80C and avoid repeated freeze-thaw cycles. Reconstituted solutions should generally be used within days to weeks depending on buffer and temperature.

Which melanocortin receptors does Melanotan II bind and with what potency?

Melanotan II is a high-affinity, non-selective melanocortin receptor agonist. Commonly cited binding affinities are approximately Ki 0.67 nM at MC1R, 6.6 nM at MC4R, 34 nM at MC3R and 46 nM at MC5R. It does not meaningfully engage MC2R, the ACTH receptor of the adrenal cortex, because MC2R requires the ACTH-specific KKRRP motif absent from alpha-MSH analogs. This receptor profile makes MT-II a useful broad-spectrum probe, best paired with subtype-selective agonists and antagonists such as SHU9119 or JKC-363 for deconvolution.

What is the plasma half-life of Melanotan II?

Melanotan II has a short reported plasma half-life of roughly 33 minutes after parenteral administration, which is nevertheless substantially longer than native alpha-MSH whose half-life is measured in minutes or less. The cyclic lactam architecture and the D-phenylalanine residue are the principal determinants of this improved metabolic stability. Its pigmentary effects considerably outlast plasma exposure because melanogenesis is a downstream transcriptional process.

What purity, documentation and pack sizes are available?

Research-grade Melanotan II is supplied as a white to off-white lyophilized powder at >=98% HPLC purity. Each lot ships with a Certificate of Analysis including the RP-HPLC purity chromatogram, ESI-MS or MALDI-TOF molecular weight confirmation, amino acid or sequence verification, net peptide content, water content and counter-ion (acetate/TFA) determination. Catalog pack sizes are 1 g, 5 g, 10 g, 100 g and 1 KG, with the first four tiers in stock and the 1 KG industrial tier made to order.

Melanotan II (MT-II) CAS 121062-08-6 | Melanocortin Receptor Agonist Peptide, 98% HPLC Tanning Peptide

Melanotan II CAS 121062-08-6
Cyclic Melanocortin Receptor Agonist Peptide

Name: Melanotan II
Brand: Nutrabiotech Chem
SKU: MT2-121062
Price: Inquiry USD
Availability: InStock

A synthetic cyclic lactam heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH) developed at the University of Arizona. Melanotan II (MT-II, MT2) is a high-affinity, non-selective agonist across MC1R, MC3R, MC4R and MC5R — driving eumelanin synthesis in melanocytes via MC1R, and central MC3R/MC4R pathways governing sexual arousal and energy balance. The definitive research peptide for melanocortin system pharmacology.

Melanocortin Agonist MC1R Ki 0.67 nM Cyclic Lactam Heptapeptide α-MSH Analog Eumelanin / Pigmentation MC4R Energy Balance ≥98% HPLC Lyophilized

Request a Quote Technical Specs

1024.18

MW (C50H69N15O9)

≥98%

Purity (HPLC)

4 Receptors

MC1R/MC3R/MC4R/MC5R

Molecular Information

Name: Melanotan II (MT-II)
CAS: 121062-08-6
Formula: C50H69N15O9
MW: 1024.18 g/mol
Purity: ≥98% (HPLC)
Sequence: Ac-Nle-cyclo[Asp-His-
D-Phe-Arg-Trp-Lys]-NH2
Cyclization: Asp²–Lys⁷ lactam bridge
InChIKey: JDKLPDJLXHXHNV
-MFVUMRCOSA-N
Appearance: White lyophilized powder
Solubility: Water, acetic acid, DMSO
Synonyms: MT-II / MT2 / Melanotan 2
Storage: -20°C, protect from light

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CAS Number

121062-08-6

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Molecular Weight

1024.18

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Primary Target

MC1R / MC4R

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Purity

≥98% HPLC

Melanotan II Technical Specifications & Peptide QC Data

Complete physicochemical and quality control parameters for research-grade Melanotan II lyophilized peptide (CAS 121062-08-6, MT-II)

📋 Peptide & Physicochemical Properties

Product NameMelanotan II
Sequence (one-letter)Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
ModificationsN-terminal acetyl; Nle¹; D-Phe⁴; C-terminal amide; Asp²–Lys⁷ lactam
CAS Number121062-08-6
SynonymsMT-II / MT2 / Melanotan 2
Molecular FormulaC50H69N15O9
Molecular Weight1024.18 g/mol
Peptide Length7 residues (cyclic)
PharmacophoreHis-D-Phe-Arg-Trp core
InChIKeyJDKLPDJLXHXHNV-MFVUMRCOSA-N
AppearanceWhite to off-white lyophilized powder
Reported Half-life~33 minutes (parenteral)
Predicted pKa13.00 ± 0.70
PubChem CID92432

🔬 Quality Control & Handling

Purity (RP-HPLC)≥98%
Identity ConfirmationESI-MS / MALDI-TOF
Net Peptide ContentReported per lot on COA
Counter-ionAcetate (TFA level reported)
FormLyophilized powder / cake
Storage Condition-20°C, sealed, dry, protect from light
SolubilityWater; dilute acetic acid; DMSO; sterile saline / PBS
ReconstitutionAliquot, store -20/-80°C, avoid freeze-thaw
Hazard ClassificationXn; H302 (harmful if swallowed)
QC DocumentationCOA / HPLC / MS / MSDS
Pack Sizes1g / 5g / 10g / 100g / 1KG
Stock StatusIn Stock
Use StatementResearch use only; not approved for human use in any country

Melanocortin Receptor Targets & Signaling Partners

Melanotan II engages four of the five melanocortin receptor subtypes with nanomolar affinity — MC2R (the ACTH receptor) is not activated because it requires the ACTH-specific KKRRP motif absent from α-MSH analogs

🎯 MC1R — Ki ~0.67 nM (Pigmentation) 🧠 MC4R — Ki ~6.6 nM (Appetite/Libido) ⚡ MC3R — Ki ~34 nM (Energy Balance) 💧 MC5R — Ki ~46 nM (Exocrine Glands) 🚫 MC2R (Not Activated) 💠 Gs / Adenylyl Cyclase 🔑 cAMP / PKA 🧬 CREB Phosphorylation ⭐ MITF Master Regulator 🎨 Tyrosinase / TRP-1 / TRP-2 🍽️ POMC / AgRP Circuits 🧫 Eumelanin Synthesis

How Melanotan II Works: From Cyclic Peptide to Melanocortin Signaling

A stepwise view of receptor engagement, cAMP signaling and the divergent peripheral and central outcomes of melanocortin agonism

Conformationally Locked Pharmacophore

The Asp²–Lys⁷ lactam bridge rigidly constrains the essential His-D-Phe-Arg-Trp message sequence into its bioactive β-turn, delivering superpotency over native α-MSH and strong resistance to peptidase degradation.

Melanocortin Receptor Binding

MT-II binds MC1R, MC3R, MC4R and MC5R — all class A Gs-coupled GPCRs — with nanomolar affinity. Receptor distribution, not intrinsic selectivity, determines which physiological system responds.

cAMP Elevation & PKA Activation

Gs coupling stimulates adenylyl cyclase, raising intracellular cAMP and activating protein kinase A, which phosphorylates the transcription factor CREB in target cells.

MC1R → MITF → Eumelanogenesis

In epidermal melanocytes, CREB drives MITF expression, the master melanocyte transcription factor, upregulating tyrosinase, TRP-1 and TRP-2 and shifting pigment synthesis toward dark eumelanin — UV-independent skin darkening.

Central MC4R/MC3R Circuits

In the hypothalamus, MC4R activation in the paraventricular nucleus suppresses food intake and raises energy expenditure, while melanocortin signaling in spinal and hypothalamic pathways modulates sexual arousal and erectile function.

Downstream Physiological Outcomes

The combined result is increased skin pigmentation, altered appetite and energy balance, modulated sexual function, and MC5R-dependent exocrine/sebaceous gland effects — a broad phenotype reflecting MT-II's non-selective profile.

Research Applications of Melanotan II (MT-II)

The reference broad-spectrum melanocortin agonist across dermatology, neuroendocrinology, metabolism and peptide chemistry

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Skin Pigmentation & Melanogenesis Research

The classic application. Used in B16 murine melanoma, human epidermal melanocyte and reconstructed skin models to quantify tyrosinase activity, melanin content, MITF induction and the eumelanin-to-pheomelanin ratio — including UV-independent photoprotection hypotheses.

MC1R / Melanocytes

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Melanocortin System Pharmacology

A benchmark agonist for mapping the POMC/α-MSH/AgRP axis. Standard workflows include cAMP accumulation assays across MC1R-MC5R, competition binding against ¹²⁵I-NDP-MSH, and pairing with antagonists such as SHU9119 and agouti-related protein for receptor deconvolution.

GPCR Probe

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Appetite, Obesity & MC4R Energy Balance

MC4R is the most important monogenic obesity gene in humans. MT-II is widely used to probe hypothalamic feeding circuits, food intake suppression, body weight and energy expenditure in rodent models, and as a positive control against MC4R-selective agents such as setmelanotide.

Metabolic Research

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Sexual Function & Erectile Physiology

Melanocortin-induced erectile activity is centrally mediated and independent of the NO/cGMP pathway. Used in ex copula erection assays, spinal proerectile circuit mapping and lordosis behaviour studies — research that ultimately produced the MC4R-selective analog bremelanotide.

Neuroendocrinology

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Peptide Chemistry & Conformational Design

A textbook case study in cyclization strategy: side-chain-to-side-chain lactam bridging, D-amino acid substitution and terminal capping to convert a labile linear hormone into a superpotent, protease-resistant therapeutic lead. Used in SAR, NMR conformational and molecular docking studies.

Peptide Engineering

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Anti-inflammatory & Neuroprotection

Melanocortin receptor activation exerts anti-inflammatory effects on microglia and macrophages via NF-κB suppression. MT-II has been reported to promote peripheral nerve regeneration and display neuroprotective properties in rat models, expanding interest in MC receptors as immune targets.

Neuroimmunology

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MC5R, Sebaceous & Exocrine Gland Biology

MC5R is enriched in sebaceous, lacrimal, harderian and preputial glands. MT-II serves as an agonist tool for studying sebum production, lipid secretion, exocrine gland differentiation and potential relevance to acne and dry-eye research.

MC5R Biology

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Receptor Structural Biology

Used as a reference ligand in cryo-EM and crystallographic studies of melanocortin receptor–Gs complexes, in mutagenesis mapping of the transmembrane binding pocket, and in calcium-dependent ligand recognition studies unique to the MC receptor family.

Structural Pharmacology

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Analytical Reference & Peptide Bioanalysis

Supplied as a reference standard for LC-MS/MS peptide quantification, RP-HPLC method development, purity and impurity profiling, counter-ion and net peptide content determination, and stability-indicating assay validation for cyclic peptides.

Reference Standard

Key Publications on Melanotan II & Melanocortin Peptides

From the original University of Arizona cyclic lactam design work through pilot clinical tanning and sexual function studies

Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Potent and prolonged acting cyclic lactam analogues of α-melanotropin: design based on molecular dynamics. Journal of Medicinal Chemistry. 1989;32(12):2555-2561. (The original design and synthesis of MT-II.)

doi: 10.1021/jm00132a010

Levine N, Sheftel SN, Eytan T, et al. Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin. JAMA. 1991;266(19):2730-2736.

doi: 10.1001/jama.1991.03470190078033

Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sciences. 1996;58(20):1777-1784.

doi: 10.1016/0024-3205(96)00160-9

Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo controlled crossover study. The Journal of Urology. 1998;160(2):389-393.

doi: 10.1016/S0022-5347(01)62903-3

Dorr RT, Ertl G, Levine N, et al. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Archives of Dermatology. 2004;140(7):827-835.

doi: 10.1001/archderm.140.7.827

Hadley ME, Dorr RT. Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides. 2006;27(4):921-930.

doi: 10.1016/j.peptides.2005.01.029

Melanotan II Pack Sizes & Ordering Information

Research-grade Melanotan II lyophilized peptide (CAS 121062-08-6) available in 1g / 5g / 10g / 100g / 1KG with full peptide QC documentation

Tier	Pack Size	Stock Status	Suitable For	Lead Time & Shipping
Standard	1 g	In Stock	Receptor binding and cAMP assays, melanocyte culture studies	Same/next-day ship; cold pack, light-protected vial
Medium	5 g	In Stock	Rodent feeding, pigmentation and behavioural pharmacology	Same/next-day ship; insulated cold chain
Large	10 g	In Stock	Extended in vivo programs, multi-site collaborations	Same/next-day ship; DHL/FedEx cold chain
Bulk	100 g	In Stock	Peptide formulation and lyophilization development, scale-up	Quote to confirm; foil pouch with desiccant, dry ice
Industrial	1 KG	Made to order	Pilot/production scale SPPS campaigns, CMO supply contracts	Scheduled batch delivery; validated cold-chain freight

💡 Reference sizes shown above; Melanotan II is supplied as a lyophilized peptide under cold-chain conditions. For exact bulk pricing please contact us for a quote. Bulk orders qualify for tiered discounts.

Melanotan II FAQ — Frequently Asked Questions

What is Melanotan II (CAS 121062-08-6)?

Melanotan II (MT-II, MT2) is a synthetic cyclic lactam heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH), designed at the University of Arizona in the late 1980s by Hruby, Hadley and colleagues. Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂, molecular formula C50H69N15O9, molecular weight 1024.18 g/mol. It is a potent non-selective agonist at MC1R, MC3R, MC4R and MC5R. It is offered strictly as a research chemical.

What is the difference between Melanotan I (afamelanotide) and Melanotan II?

Melanotan I / afamelanotide is a linear 13-residue α-MSH analog ([Nle⁴, D-Phe⁷]-α-MSH) that is comparatively MC1R-preferring, so its activity is largely confined to pigmentation; it has been developed into an approved subcutaneous implant for erythropoietic protoporphyria. Melanotan II is a shorter cyclic heptapeptide — more potent but markedly less selective, hitting MC1R, MC3R, MC4R and MC5R. That broader coverage is exactly why MT-II produces effects beyond tanning, notably MC4R-mediated changes in sexual arousal and appetite.

How does Melanotan II produce skin tanning at the molecular level?

MT-II activates MC1R on epidermal melanocytes. MC1R is Gs-coupled, so agonism raises cAMP → activates PKA → phosphorylates CREB → upregulates MITF, the master melanocyte transcription factor. MITF then drives tyrosinase, TRP-1 and TRP-2 expression, shifting the melanogenic pathway toward dark eumelanin rather than red-yellow pheomelanin. Critically, this occurs without UV exposure, which is what made "tanning peptides" a research curiosity in the first place.

Why does the same peptide affect both tanning and libido?

Because it is non-selective and different melanocortin receptors sit in different tissues. MC1R in skin controls pigmentation. MC4R and MC3R in the hypothalamus and spinal cord regulate energy balance and sexual arousal — melanocortin-induced erectile activity is centrally mediated and independent of the NO/cGMP pathway used by PDE5 inhibitors. Recognising this split led directly to the development of the MC4R-selective analog bremelanotide (PT-141) for sexual dysfunction and MC4R-selective agents for obesity.

What does the Asp–Lys lactam bridge actually do?

The bridge is an amide bond between the side-chain carboxyl of Asp² and the ε-amino group of Lys⁷. This side-chain-to-side-chain cyclization locks the His-D-Phe-Arg-Trp message sequence into its bioactive β-turn conformation, which raises receptor affinity by orders of magnitude and prolongs action. It also removes free termini and constrains the backbone, giving strong resistance to exopeptidase and endopeptidase degradation. The D-Phe⁴ substitution adds further proteolytic stability — a classic peptide engineering combination.

How stable is Melanotan II and how should it be reconstituted and stored?

The lyophilized powder is very stable when stored sealed at -20°C, dry and protected from light. It dissolves in water, dilute acetic acid and DMSO, and can be diluted into sterile saline or PBS; a small volume of dilute acetic acid helps with stubborn dissolution before buffer dilution. Once reconstituted, aliquot into single-use low-binding vials, store at -20°C or -80°C and avoid repeated freeze-thaw cycles. Reconstituted solutions are far less stable than the dry cake and should be used within days to weeks depending on buffer, pH and temperature.

Which melanocortin receptors does MT-II bind, and does it hit MC2R?

Reported binding affinities are approximately MC1R Ki 0.67 nM, MC4R 6.6 nM, MC3R 34 nM and MC5R 46 nM. It does not meaningfully activate MC2R, the adrenal ACTH receptor, because MC2R uniquely requires the ACTH-specific KKRRP motif that α-MSH analogs lack — so MT-II does not stimulate corticosteroid release. For subtype attribution, pair MT-II with selective tools such as SHU9119 (MC3R/MC4R antagonist) or agouti-related protein.

What is the half-life of Melanotan II?

The reported plasma half-life is roughly 33 minutes after parenteral administration — short in absolute terms, but far longer than native α-MSH, which is degraded within minutes. The cyclic lactam scaffold and D-amino acid substitution account for this improvement. Note that pigmentary effects substantially outlast plasma exposure, because melanogenesis is a downstream transcriptional and enzymatic process operating over days, not minutes — an important consideration when designing dosing schedules in animal models.

Is Melanotan II approved for human use anywhere?

No. Melanotan II has never been approved for human use in any country, and regulatory agencies in multiple jurisdictions have issued public warnings about unregulated cosmetic tanning products containing it. Material supplied by Nutrabiotech Chem is intended exclusively for laboratory research by qualified professionals — it is not for human consumption, cosmetic, diagnostic or therapeutic use. Purchasers confirm lawful research use at the point of order.

What peptide QC documentation do you provide with each lot?

Every lot ships with a Certificate of Analysis (COA) containing the RP-HPLC purity chromatogram (≥98%), ESI-MS or MALDI-TOF molecular weight confirmation, sequence/amino acid verification, net peptide content, water content and counter-ion (acetate/TFA) levels. MSDS/SDS, solubility guidance and Certificate of Origin are available on request. Pack sizes are 1 g, 5 g, 10 g, 100 g and 1 KG — contact us for bulk peptide synthesis quotations.

Need Melanotan II (CAS 121062-08-6) for Your Research?

Research-grade Melanotan II / MT-II lyophilized peptide — purity ≥98% HPLC, COA with MS confirmation, 1g to 1KG
The reference cyclic melanocortin agonist for pigmentation, MC4R and peptide engineering research — request a quote today

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Weight	1 g

CAS 121062‑08‑6 Melanotan II Powder Cyclic α‑MSH Peptide for Skin‑Pigmentation and MC‑Receptor Pharmacology Research