Melanotan 2 (Melanotan II) — Non-Selective Melanocortin Agonist (MC1R/MC3R/MC4R/MC5R)
Research-Grade Compound
Melanotan 2 (also written Melanotan II, or MT-2) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone that acts as a non-selective agonist at four of the five melanocortin receptors: MC1R, MC3R, MC4R and MC5R. Molecular formula C50H69N15O9, molecular weight 1,024.2 Da, CAS 121062-08-6. Structure: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2.
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What is Melanotan II?
Melanotan 2 (also written Melanotan II, or MT-2) is a synthetic cyclic heptapeptide analog of α-melanocyte-stimulating hormone that acts as a non-selective agonist at four of the five melanocortin receptors: MC1R, MC3R, MC4R and MC5R. Molecular formula C50H69N15O9, molecular weight 1,024.2 Da, CAS 121062-08-6. Structure: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2.
The design is a conformational constraint exercise. Native α-MSH is a linear 13-residue POMC-derived neuropeptide whose activity depends on a four-residue core, His-Phe-Arg-Trp, adopting a specific turn geometry at the receptor. Melanotan II locks that turn by closing a ring between the aspartate side-chain carboxyl and the lysine side-chain amine, and substitutes D-phenylalanine for the L-form. The bridge is a lactam, not a disulfide — a detail misreported often enough to be worth stating plainly. The result is a molecule with higher affinity and far greater resistance to proteolysis than the linear parent.
Melanotan II is not approved by the FDA for any indication, in any country it is not a licensed medicine sold over the counter, and it is prohibited by the World Anti-Doping Agency. Medicines regulators — the UK MHRA among them — have issued public warnings about unlicensed melanotan tanning products sold online. Peptide.Express supplies Melanotan II strictly as a research compound for in-vitro laboratory use, and the regulatory picture above is part of the compound record rather than a footnote to it.
How Does Melanotan II Work? Mechanism of Action
All five melanocortin receptors are Gs-coupled GPCRs that raise intracellular cAMP on activation. What differs between them is where they are expressed and what PKA phosphorylates once cAMP rises. Melanotan II engages four of the five, which is simultaneously the reason it is useful as a broad melanocortin tool compound and the reason its results are difficult to attribute.
MC1R is the melanocyte receptor and the best-characterised branch. Agonism raises cAMP, PKA phosphorylates CREB, CREB drives transcription of MITF (microphthalmia-associated transcription factor), and MITF in turn upregulates tyrosinase, TRP-1 and TRP-2 — the enzymatic machinery of melanin synthesis. The shift is toward eumelanin over pheomelanin. In cell culture this cascade is measurable at every step, which is why B16 murine melanoma preparations remain the standard melanogenesis assay system.
MC3R and MC4R are the central receptors, concentrated in the arcuate and paraventricular hypothalamic nuclei and adjacent limbic structures. Activation there feeds into energy-balance and arousal circuitry rather than pigmentation. MC5R sits largely in exocrine tissue, including sebaceous glands, where it participates in secretory regulation. One compound, four receptors, four unrelated output systems.
The design consequence is unavoidable: an observed effect cannot be assigned to a receptor without help. Selective antagonists such as SHU9119 for MC3R/MC4R, receptor-null models, or single-receptor recombinant cell lines are the usual approaches. Protocols that administer Melanotan II systemically and then measure one downstream endpoint are measuring the sum of four pathways, not one. Separately, human pharmacokinetic data for this compound is thin — most of what circulates about its behaviour in humans derives from uncontrolled use rather than from trials, and that gap should be treated as a real limit on interpretation.
Research Applications of Melanotan II
Melanogenesis and MC1R Pathway Research
- Tyrosinase induction assays: B16 murine melanoma cells provide the standard readout for MC1R-driven melanin synthesis, with tyrosinase activity measured directly.
- Transcriptional cascade mapping: cAMP response element binding protein phosphorylation and MITF expression are the intermediate markers linking receptor occupancy to pigment output.
- Eumelanin to pheomelanin ratio quantification: the qualitative shift in melanin type, rather than total melanin, is often the more informative endpoint.
Comparative Melanocortin Receptor Pharmacology
- Receptor selectivity mapping: cAMP accumulation in cell lines expressing single recombinant receptors places Melanotan II against selective agonists across the MC1R–MC5R panel.
- Structure-activity comparison with PT-141: the carboxamide versus free-acid C-terminus is a single-variable experiment on melanocortin selectivity.
- Antagonist attribution studies: SHU9119 and agouti-related peptide are used to subtract the MC3R/MC4R contribution from a mixed signal.
Melanocyte Proliferation and Safety-Relevant Models
- Melanocytic nevus research: case reports have described changes in melanocytic naevi in the context of unlicensed melanotan use, and preclinical models examining melanocyte proliferation follow from that observation. Causality has not been established.
- Proliferation versus differentiation endpoints: distinguishing pigment production from melanocyte division is the mechanistic question these models are built to answer.
- UV-response interaction studies: MC1R signalling and UV-triggered melanogenesis converge on overlapping transcriptional targets, so co-exposure designs require careful controls.
Melanotan II vs PT-141 (Bremelanotide)
| Feature | Melanotan II | PT-141 (Bremelanotide) |
|---|---|---|
| Structure | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 | Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH |
| C-terminus | Carboxamide | Free acid |
| Molecular formula | C50H69N15O9 | C50H68N14O10 |
| Molecular weight | 1,024.2 Da | 1,025.2 Da |
| CAS number | 121062-08-6 | 189691-06-3 |
| Receptor profile | MC1R, MC3R, MC4R, MC5R | Preferential MC3R / MC4R |
| Melanogenesis relevance | Direct MC1R agonism — primary research readout | Residual MC1R affinity only |
| Exocrine (MC5R) activity | Present | Not a primary target |
| FDA status | Not approved for any indication | Approved as Vyleesi for HSDD in premenopausal women |
| WADA status | Prohibited | Approved drug product; research material sold for laboratory use only |
A third molecule is routinely confused with both: Melanotan I, generic name afamelanotide, which is a linear 13-residue α-MSH analog rather than a cyclic heptapeptide. It is MC1R-preferring, lacks the broad central receptor activity of Melanotan II, and is marketed as Scenesse for erythropoietic protoporphyria. Melanotan I and Melanotan II share a naming convention and almost nothing else — different structure class, different selectivity, different regulatory status.
Melanotan II Technical Specifications
| Compound Name | Melanotan II (MT-II) |
|---|---|
| Common Synonyms | Melanotan 2, MT-2, MT-II, melanotan-2 |
| Classification | Cyclic heptapeptide α-MSH analog, non-selective melanocortin agonist |
| Amino Acid Sequence | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 |
| Ring Chemistry | Lactam bridge between the Asp side-chain carboxyl and the Lys side-chain amine |
| Receptor Targets | MC1R, MC3R, MC4R, MC5R |
| Parent Neuropeptide | α-melanocyte-stimulating hormone (POMC-derived, 13 residues) |
| CAS Number | 121062-08-6 |
| Molecular Formula | C50H69N15O9 |
| Molecular Weight | 1,024.2 Da |
| Purity | ≥99% by HPLC |
| Purity Confirmation | LC-MS/MS molecular weight verification |
| Endotoxin Testing | LAL (Limulus Amebocyte Lysate) method |
| Physical Form | Lyophilized powder |
| Appearance | White to off-white powder |
| Reconstitution | Bacteriostatic water or sterile 0.9% sodium chloride |
| Storage (lyophilized) | -20°C, desiccated, protected from light |
| Storage (reconstituted) | 2–8°C, use within 14–28 days |
| Shelf Life | 24 months from manufacture (lyophilized) |
| Testing Methods | HPLC, LC-MS/MS, LAL Endotoxin |
| Documentation | Certificate of Analysis (CoA) per batch |
| FDA Status | Not approved for any indication |
| WADA Status | Falls under section S0 (non-approved substances) — no marketing authorisation in any jurisdiction |
| Intended Use | In-vitro laboratory research only |
How to Reconstitute Melanotan II for Research
Melanotan II and PT-141 differ by about 1 Da and look identical as lyophilized powder. Label vials at the moment of reconstitution, not afterwards. If two melanocortin compounds are open on the same bench, the only thing separating them is the writing on the glass.
- Allow the vial to reach room temperature before opening.
- Draw the calculated volume of bacteriostatic water. For a 10 mg vial, 2 mL yields 5 mg/mL and 5 mL yields 2 mg/mL.
- Swab the septum with alcohol and allow 30 seconds to dry.
- Inject the diluent slowly against the inner vial wall, not onto the lyophilized cake.
- Swirl gently for 60–90 seconds. Do not shake and do not vortex.
- Verify that the solution is clear and colorless with no visible particulate. Discard if cloudy or discolored.
- Label with the compound name, reconstitution date and resulting concentration.
- Store at 2–8°C, use within 14–28 days, and avoid repeated freeze-thaw cycles.
Diluent: bacteriostatic water for peptide reconstitution. Full protocol: step-by-step peptide reconstitution guide. Concentration maths: peptide reconstitution calculator.
Frequently Asked Questions — Melanotan II
What is Melanotan II?
What melanocortin receptors does MT-II activate?
How does Melanotan II drive melanogenesis at the molecular level?
What is the difference between Melanotan II and PT-141?
What is the difference between Melanotan 1 and Melanotan 2?
Is Melanotan II FDA approved?
Is Melanotan II WADA prohibited?
Have regulators issued warnings about melanotan products?
What are the research considerations around melanocytes and MT-II?
Is Melanotan II legal to purchase for laboratory research?
What purity standard and testing does Peptide.Express apply to Melanotan II?
How should Melanotan II be stored before and after reconstitution?
Where is the Certificate of Analysis for Melanotan II?
Research References
- Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996. Read Dorr et al.'s first-in-human pilot study of Melanotan II
- Buscà R, Ballotti R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 2000. Read Buscà and Ballotti's review of the cAMP-CREB-MITF melanogenesis cascade
- Cousen P, Colver G, Helbling I. Eruptive melanocytic naevi following melanotan injection. Br J Dermatol. 2009. Read Cousen et al.'s case report of eruptive naevi after melanotan injection
All products are sold for in-vitro laboratory research use only. Not intended for human consumption, clinical use, or veterinary use. Peptide.Express makes no medical claims. Consult the published literature for research application guidance.