Melanotan 2 (MT-II) occupies an awkward position in the US research-compound market: one of the most searched peptides on the domestic supply side, and one of the most poorly described. Most of what circulates about it is consumer folklore attached to a molecule whose actual published record is a narrow, well-characterized body of receptor pharmacology built in frog skin, lizard skin, rodent brain and cultured melanocytes.
This article covers what that record contains, where the load-bearing experiments were done, and — the part almost nobody writes about — why MT-II’s defining pharmacological property makes it a difficult compound to design a clean experiment around. All material discussed here is supplied for research use only and is not for human use.
What the molecule is
MT-II did not emerge from a screening program. It was designed, and the design lineage is traceable through two specific papers.
The first is Sawyer and colleagues (PNAS, 1980), who reported [Nle⁴, D-Phe⁷]-α-MSH — the analog now generally called NDP-α-MSH. Substituting norleucine at position 4 and D-phenylalanine at position 7 produced a peptide resistant to enzymatic degradation by serum enzymes, roughly 26 times as potent as native α-MSH in a mouse melanoma adenylate cyclase assay, and possessed of what the authors described as ultralong biological activity in the frog skin bioassay. That paper established that the α-MSH pharmacophore could be stabilized without losing activity.
The second is Al-Obeidi, Castrucci, Hadley and Hruby (J Med Chem, 1989), who took that stabilized core and cyclized it through a lactam bridge between side-chain groups at positions 5 and 10. Seven cyclic peptides were prepared and assayed in standard Rana pipiens (frog) and Anolis carolinensis (lizard) skin bioassays. Ring size turned out to be decisive: the 23-membered ring analogs reached roughly 100-fold the melanotropic potency of α-MSH in the lizard assay, while increasing or decreasing the ring size from 23 members diminished potency. The 23- and 24-membered rings also showed prolonged residual activity that the smaller rings did not. The compound the research market calls Melanotan 2 comes out of that series.
Two things follow from this history and both matter for experimental design. MT-II is a conformationally constrained cyclic peptide, not a linear fragment, which is why it resists the proteolysis that limits native α-MSH. And its potency data originate in amphibian and reptilian pigment cell assays, which are sensitive and historically important but are not mammalian systems.
The receptor family, and the selectivity problem
The melanocortin receptors were cloned in the early 1990s — Mountjoy and colleagues (Science, 1992) reported the family, Gantz and colleagues (J Biol Chem, 1993) the fourth subtype. Five are now recognized, all class A GPCRs coupled to adenylyl cyclase, with markedly different tissue distributions: MC1R on melanocytes, MC2R as the ACTH receptor in adrenal cortex, MC3R and MC4R predominantly central, MC5R broadly in exocrine tissue.
Here is the property that defines MT-II experimentally. Schiöth and colleagues (Peptides, 1997) tested the cyclic lactam analogs MT-II and SHU9119, plus five cyclic [Cys⁴, Cys¹⁰] α-MSH analogs, on cells transiently expressing human MC1, MC3, MC4 and MC5 receptors. The cyclic lactams showed overall higher affinity for the melanocortin receptors than any of the cyclic disulfide analogs tested — but MT-II is a broad agonist across the subtypes, not an MC1R tool. Substituting D-Nal(2′)⁷ for D-Phe⁷ was what shifted selectivity toward MC4.
The practical consequence is that any in vivo readout following systemic MT-II administration in an animal model is a composite of at least four receptor populations in different organs. Attributing a pigmentation endpoint to MC1R, or a feeding endpoint to MC4R, requires a subtype-selective antagonist arm, a receptor-null model, or both. Studies that omit those controls have not isolated a mechanism, whatever their abstract says.
Central melanocortin signaling: the MC4R literature
The cleanest MT-II experiment in the published record is arguably Fan, Boston, Kesterson, Hruby and Cone (Nature, 1997). Intracerebroventricular administration of MT-II inhibited feeding in four separate models of hyperphagia in mice — fasted C57BL/6J, ob/ob, A^y, and animals injected with neuropeptide Y. Critically, co-administration of the melanocortin antagonist and agouti-mimetic SHU9119 completely blocked that inhibition, and SHU9119 alone significantly enhanced nocturnal or fast-stimulated feeding. That is a properly controlled experiment: agonist, antagonist rescue, and multiple independent models of the same phenotype.
It sits alongside two genetic pillars. Lu and colleagues (Nature, 1994) showed that agouti protein is a high-affinity antagonist of the MSH receptor, blocking α-MSH stimulation of adenylyl cyclase, and is also an antagonist at MC4R. Huszar and colleagues (Cell, 1997) showed that targeted disruption of MC4R produces obesity in mice. Together these establish that central melanocortin tone is tonically inhibitory on feeding behavior in rodents, and that MT-II engages that circuit.
Autonomic endpoints have been characterized in rats. Giuliano and colleagues (Eur Urol, 2005) implanted a pressure sensor in the corpus cavernosum of adult rats and used telemetry to monitor intracavernosal pressure in freely moving animals after intravenous MT-II at 0.1, 0.3 and 1 mg/kg or saline. At 1 mg/kg, MT-II significantly increased overall erectile activity relative to saline in conscious animals; in anaesthetized animals the same pattern appeared but did not reach statistical significance. The conscious-versus-anaesthetized divergence is the useful methodological finding — anesthesia suppressed the effect size.
Pigmentation and photoprotection: read this section carefully
This is where the literature is most often overstated, so it is worth being precise about who studied what.
The MC1R–cAMP–tyrosinase axis is well established, and there is a substantial body of work showing that melanocortin signaling in melanocytes does more than make pigment. Böhm and colleagues (J Biol Chem, 2005) showed that α-MSH blocks UVB-induced apoptosis in normal human melanocytes in vitro, and that the effect was not explained by filtering or by induction of melanin synthesis: α-MSH markedly reduced cyclobutane pyrimidine dimer formation, and the protection was absent in nucleotide-excision-repair-deficient fibroblasts, implicating repair induction rather than sunscreening. Kadekaro and colleagues (Mol Cancer Res, 2012) extended this, showing MC1R activation contributes to phosphorylation of p53 at serine 15 via cAMP/PKA, PI3K, ATR and DNA-PK, and raises levels of the base-excision-repair enzymes OGG1 and APE-1/Ref-1. Abdel-Malek and colleagues (Pigment Cell Melanoma Res, 2009) showed the same class of effects with tripeptide α-MSH analogs, and demonstrated receptor dependence directly: the effects were absent in human melanocytes expressing non-functional MC1R.
Upstream, Cui and colleagues (Cell, 2007) established that UV induction of POMC/MSH in skin is directly controlled by p53, and that p53-knockout mice lack the UV tanning response altogether.
None of those studies used MT-II. They used α-MSH and short synthetic analogs, in cultured human melanocytes and in mouse skin. It is a reasonable mechanistic hypothesis that a broad melanocortin agonist engages the same MC1R node, and it is not a demonstrated result. A research page that cites Böhm or Kadekaro as though the experiment had been run with MT-II is misrepresenting the source. We are citing them here as receptor-pathway context, explicitly labeled as such.
The regulated end of this receptor class does exist: afamelanotide, a linear α-MSH analog, has been through formal clinical development and continues to be studied in erythropoietic protoporphyria (see, for example, Seidl-Philipp et al., J Dtsch Dermatol Ges, 2026). That is a different molecule, developed under a different regulatory pathway, and the distinction is the entire point.
Why identity and purity are the live risk on this specific compound
There is a purity argument attached to MT-II that does not apply to most peptides in a research catalog, and it comes out of the dermatology literature. Cousen and colleagues (Br J Dermatol, 2009) reported eruptive melanocytic naevi following injection of material sold as melanotan, and comparable case reports followed in Scandinavia (Burian et al., Läkartidningen, 2013). The recurring feature in those reports is unregulated gray-market material of unknown composition — not a characterized research-grade compound with an analytical record behind it.
For a US laboratory sourcing MT-II, that translates into a short list. Identity confirmed by mass spectrometry against the expected molecular weight for the cyclic lactam, not assumed from a label. Purity reported by HPLC with the chromatogram available, not asserted as a number. A batch-specific COA traceable to the lot in the vial, because a certificate that does not name the lot certifies nothing. And net peptide content, since residual counterion and water contribute mass that a purity percentage alone does not disclose.
Sourcing in the United States
Maple Research Labs stocks this compound domestically. Vials ship same-day from our Santa Barbara facility — for a US research group, the difference between a Tuesday delivery and an overseas parcel of uncertain provenance sitting in a customs queue for three weeks with no temperature record. The entity is registered in Sheridan, Wyoming, and every lot is traceable to its supplier and its certificate of analysis. Storage follows the usual conventions for lyophilized research peptides: sealed vial cold and dark, minimal freeze–thaw cycling, lot and receipt date recorded against the COA on file.
Melanotan 2 10mg with batch COA is listed with its HPLC purity report and lot number.
Summary
MT-II is a conformationally constrained cyclic lactam analog of α-MSH, designed from the NDP-α-MSH scaffold, with potency data grounded in amphibian and reptile pigment-cell bioassays and receptor pharmacology in transfected human cells. Its best-controlled in vivo work is central: MC4R-mediated suppression of feeding in four murine hyperphagia models, reversed by SHU9119. Its autonomic effects are documented by telemetry in conscious rats. Its photoprotective mechanism is extrapolated from α-MSH studies in cultured human melanocytes rather than demonstrated with MT-II itself, and should be described that way. The compound’s broad receptor coverage is not a footnote — it is why any serious design built around it needs antagonist or receptor-null controls before a mechanistic claim can be made.
All products and information supplied by Maple Research Labs are for research use only. These materials are not for human use or consumption, and nothing on this page describes or recommends administration to humans.
References
- Sawyer TK, et al. 4-Norleucine, 7-D-phenylalanine-α-melanocyte-stimulating hormone: a highly potent α-melanotropin with ultralong biological activity. PNAS 1980;77:5754–8. PMID 6777774.
- Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Potent and prolonged acting cyclic lactam analogues of α-melanotropin. J Med Chem 1989;32:2555–61. PMID 2555512.
- Mountjoy KG, et al. The cloning of a family of genes that encode the melanocortin receptors. Science 1992;257:1248–51. PMID 1325670.
- Gantz I, et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 1993;268:15174–9. PMID 8392067.
- Schiöth HB, et al. Selectivity of cyclic [D-Nal7] and [D-Phe7] substituted MSH analogues for the melanocortin receptor subtypes. Peptides 1997;18:1009–13. PMID 9357059.
- Lu D, et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 1994;371:799–802. PMID 7935841.
- Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997;385:165–8. PMID 8990120.
- Huszar D, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997;88:131–41. PMID 9019399.
- Giuliano F, et al. The use of telemetry technology to test the proerectile effect of melanotan-II (MT-II) in conscious rats. Eur Urol 2005;48:145–51. PMID 15967265.
- Böhm M, et al. α-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage. J Biol Chem 2005;280:5795–802. PMID 15569680.
- Abdel-Malek ZA, et al. α-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. Pigment Cell Melanoma Res 2009;22:635–44. PMID 19558415.
- Kadekaro AL, et al. α-Melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes. Mol Cancer Res 2012;10:778–86. PMID 22622028.
- Cui R, et al. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 2007;128:853–64. PMID 17350573.
- Cousen P, et al. Eruptive melanocytic naevi following melanotan injection. Br J Dermatol 2009;161:707–8. PMID 19575725.
- Burian E, et al. Eruptive nevi after injection of drugs marketed as melanotan II. Läkartidningen 2013;110:96–7. PMID 23451671.
- Seidl-Philipp M, et al. Afamelanotide improves quality of life and light tolerance in Austrian erythropoietic protoporphyria patients. J Dtsch Dermatol Ges 2026. PMID 41793078.