Melanotan Peptides and the Melanocortin Agonist Family: A Research Review of α-MSH, Melanotan I, Melanotan II, Bremelanotide and Setmelanotide and the Catalogue Nomenclature Behind the "Tanning Peptide" Label

By the Peptide Insider Research Desk · 12 min read · Last updated: September 13, 2026

Melanotan I (afamelanotide, MT-1) and Melanotan II (MT-2) are synthetic analogues of α-melanocyte-stimulating hormone (α-MSH), the 13-residue proopiomelanocortin (POMC) fragment that activates the melanocortin 1 receptor (MC1R) on melanocytes [1,2,3]. Both were designed in the 1980s at the University of Arizona to resist enzymatic degradation and to prolong receptor occupancy, and both are now catalogued under a dense thicket of notations — mt2, mt2 peptide, mt-ii peptide, melanotan 2 peptide, mt1, mt-1 peptide, melanotan peptide and the colloquial umbrella term tanning peptides [1,4]. This review is a companion to the site's single-compound Melanotan II and Melanotan I reviews. It places the two compounds in the wider melanocortin agonist family — α-MSH itself, bremelanotide (PT-141) and setmelanotide — compares their receptor-selectivity profiles, and documents the catalogue and search notations that refer to each. All content is provided strictly for research reference.

Introduction

The melanocortin agonists occupy an unusual position in the research-peptide catalogue. Two members of the family — afamelanotide (Scenesse) and bremelanotide (Vyleesi) — are approved medicines with published phase 3 trials, and a third, setmelanotide (Imcivree), is approved for rare genetic obesity syndromes [9,10,11]. Yet the same molecular scaffold circulates under informal names such as peptide melanotan, peptides melanotan, peptide melanotan 2 and peptides melanotan 2, and the unregulated distribution of melanotan peptides has itself become the subject of dermatology and public-health literature [4,12]. The result is a nomenclature that mixes International Nonproprietary Names, laboratory code names and abbreviations that differ by a single hyphen.

This article covers receptor selectivity across the family, the origin of the linear and cyclic Arizona analogues, and the catalogue notations — from mt-ii peptide to peptide melanotan ii — that refer to the same peptides.

Biological background: POMC, α-MSH and the five melanocortin receptors

α-MSH is cleaved from POMC in the pituitary intermediate lobe, hypothalamic neurons and skin keratinocytes. Its sequence is Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂; the central His-Phe-Arg-Trp tetrapeptide is the minimal pharmacophore recognised by all melanocortin receptors [1,3]. In 1992 Mountjoy and colleagues cloned the receptor family and showed that the melanocortin receptors are rhodopsin-class G protein-coupled receptors that signal through G_s and adenylyl cyclase [2]. Five subtypes are now recognised [2,3]:

• MC1R — melanocytes; cAMP → PKA → CREB → MITF → tyrosinase transcription, shifting melanogenesis toward eumelanin [3,13].
• MC2R — adrenal cortex; responds to ACTH only, not to α-MSH or its analogues [2,3].
• MC3R — hypothalamus, limbic system; energy homeostasis [3].
• MC4R — hypothalamic paraventricular nucleus; appetite, erectile and autonomic responses [3,10,11].
• MC5R — exocrine glands; sebaceous and lacrimal secretion [3].

Two endogenous antagonists, agouti-signalling protein (MC1R) and agouti-related protein (MC3R/MC4R), complete the system [3]. Because an agonist that engages MC3R–MC5R as well as MC1R produces effects well beyond pigmentation, receptor selectivity is the property that most clearly distinguishes the family members [3,7].

Structure and mechanism: from α-MSH to the Arizona analogues

Native α-MSH has a plasma half-life of minutes because its Met⁴ is oxidised and its Phe⁷–Arg⁸ bond is cleaved by serum proteases [1,5]. In 1980 Sawyer, Hruby and Hadley reported that replacing Met⁴ with norleucine and L-Phe⁷ with D-Phe⁷ produced [Nle⁴,D-Phe⁷]-α-MSH, an analogue roughly 26-fold more potent than α-MSH in adenylate cyclase assays and with "ultralong" activity in the frog-skin bioassay [5]. This linear peptide was later named Melanotan I and, as afamelanotide, became the first approved melanocortin agonist [1,9].

Al-Obeidi, Hruby and colleagues then used molecular-dynamics modelling to constrain the active His-D-Phe-Arg-Trp turn. Their 1989 cyclic lactam, Ac-Nle⁴-cyclo[Asp⁵,D-Phe⁷,Lys¹⁰]-α-MSH(4–10)-NH₂, bridged the Asp⁵ and Lys¹⁰ side chains, deleted residues 1–3 and 11–13, and produced a heptapeptide that retained superpotent agonism while gaining resistance to trypsin and chymotrypsin [6]. This is Melanotan II [1,6]. Two consequences followed from cyclisation: the truncated scaffold lost MC1R selectivity and became a potent agonist at MC3R, MC4R and MC5R [7,8], and its conformational rigidity made it a template for later MC4R-directed drugs [1,10]. Bremelanotide is Melanotan II with the C-terminal amide replaced by a free carboxylic acid (the "PT-141" metabolite), and setmelanotide is a cyclic octapeptide built on the same D-Phe-Arg-Trp turn with an engineered preference for MC4R [1,10,11].

Nomenclature and catalogue variants

Two compounds, four INN or code names, and a habit of abbreviating "Melanotan" to "MT" with or without Roman numerals explain most of the notational drift. The table interprets the variants that appear in research catalogues and search queries; none represents a chemically distinct entity.

Catalogue / query string	Interpretation	Notes
melanotan-2 · melanotan 2 · melanotan ii · MT-II	Melanotan II, the cyclic lactam heptapeptide	Arabic and Roman numeral forms are interchangeable; the INN of its C-terminal acid metabolite is bremelanotide [1,6].
mt2 · mt-2 · mt 2 · MT-II	Abbreviated Melanotan II	"MT" abbreviates Melanotan; hyphen and space variants are identical. Not to be confused with MT-2 as a metallothionein isoform in the biochemistry literature.
mt2 peptide · mt 2 peptide · mt-ii peptide · mt2 peptides	Abbreviation + "peptide(s)" suffix	Redundant chemically (the compound is a peptide) but common in listings.
peptide mt2 · peptides mt2	Prefix-order variant	Search-engine word order; same compound.
melanotan 2 peptide · peptide melanotan 2 · peptides melanotan 2 · peptide melanotan ii	Full name + "peptide(s)" in either order	All denote Melanotan II.
melanotan-1 · melanotan i · melanotan 1 · MT-1 · mt1 · mt-1 peptide	Melanotan I, the linear [Nle4,D-Phe7]-α-MSH	INN afamelanotide; approved as Scenesse for erythropoietic protoporphyria [9].
melanotan peptide · melanotan peptides · peptide melanotan · peptides melanotan	Family-level terms without a numeral	Ambiguous: may refer to either analogue or to both. Catalogue context usually resolves it.
tanning peptides	Colloquial umbrella label	Informal grouping of MC1R-active analogues by their pigmentation pharmacology; not a chemical class and not a use recommendation [4,12].
melanotan 2 reddit	Discussion-forum query	Refers to anecdotal forum threads, which are not a substitute for the peer-reviewed literature cited here and are not a protocol source.

The melanocortin agonist family: receptor selectivity compared

The table summarises how the principal synthetic agonists differ in structure and receptor profile. Selectivity values are drawn from radioligand binding and cAMP assays reported in the cited literature and are approximate; absolute affinities vary with cell system and assay format [7,8].

Compound (code / INN)	Structure	Receptor profile	Development status
α-MSH (endogenous)	Linear 13-mer, Ac-Ser1...Val13-NH2	Agonist at MC1R, MC3R, MC4R, MC5R; inactive at MC2R [2,3]	Endogenous hormone; reference ligand
Melanotan I (MT-1, afamelanotide)	Linear 13-mer with Nle4, D-Phe7	Predominantly MC1R; limited CNS penetration reported [1,5,9]	Approved (Scenesse) for erythropoietic protoporphyria [9]
Melanotan II (MT-2)	Cyclic lactam heptapeptide, C-terminal amide	Non-selective agonist at MC1R, MC3R, MC4R, MC5R [7,8]	Phase I pilot studies only; not approved [1,14]
Bremelanotide (PT-141)	Melanotan II with C-terminal free acid	MC4R-favouring, retains MC1R/MC3R activity [1,10]	Approved (Vyleesi) for hypoactive sexual desire disorder [10]
Setmelanotide (RM-493)	Cyclic octapeptide, disulfide-bridged	MC4R-selective (reported ~20-fold over MC1R and MC3R) [11]	Approved (Imcivree) for POMC/LEPR-deficiency obesity [11]

Evidence by domain

The summary below is descriptive and does not endorse any use.

Domain	Compound(s)	Representative finding	Evidence level
Melanogenesis / MC1R signalling	α-MSH, MT-1, MT-2	cAMP–MITF–tyrosinase cascade; eumelanin shift [3,13]	In vitro, animal
Photoprotection in porphyria	Afamelanotide	Longer pain-free sunlight exposure in two RCTs [9]	Phase 3 RCT
Pigmentation pharmacology	MT-2	Increased skin reflectance in a 3-subject pilot [14]	Phase I pilot
Sexual function (MC4R)	MT-2, bremelanotide	Erectile responses in a crossover study [15]; HSDD phase 3 trials [10]	Crossover; phase 3 RCT
Energy homeostasis (MC4R)	Setmelanotide	Reduced hunger scores in POMC/LEPR deficiency [11]	Phase 3 single-arm
Unregulated-use safety signals	MT-1, MT-2	Reported naevus darkening, nausea, unknown product purity [4,12]	Case series, review

Melanogenesis and MC1R signalling

MC1R activation raises intracellular cAMP, activates protein kinase A and phosphorylates CREB, which drives transcription of MITF and its targets tyrosinase, TYRP1 and DCT [3,13]. In cultured melanocytes and mouse models the result is a shift from pheomelanin toward eumelanin synthesis [13]. Both Arizona analogues reproduce this cascade with higher potency and longer duration than α-MSH because of their protease resistance [5,6]. MC1R signalling has also been associated with DNA-repair responses to ultraviolet damage in preclinical work [13].

Clinical trials of the approved family members

Afamelanotide was evaluated in two randomised, placebo-controlled phase 3 trials in erythropoietic protoporphyria (n = 93 and n = 74), where participants receiving the implant reported more pain-free time in direct sunlight than placebo recipients [9]. Bremelanotide was studied in the two RECONNECT phase 3 trials (n = 1,267), which reported statistically significant changes in the Female Sexual Function Index desire domain and in desire-related distress relative to placebo, with nausea, flushing and headache as the most frequent adverse events [10]. Setmelanotide was evaluated in single-arm phase 3 trials in POMC- and LEPR-deficiency obesity, with hyperpigmentation and injection-site reactions the most frequently reported adverse events — the former a direct consequence of residual MC1R activity [11].

Melanotan II: pilot data and the unregulated-use literature

Melanotan II never progressed beyond early clinical evaluation. Dorr and colleagues published a single-blind, placebo-controlled pilot in three male volunteers that reported increased skin pigmentation by reflectance in two participants, together with nausea, somnolence, a stretching–yawning complex and spontaneous erections [14]. Wessells and colleagues subsequently reported erectile responses in a double-blind crossover study, an observation that motivated the development of bremelanotide [1,15]. The compound's later circulation through unregulated channels has been described in the BMJ and reviewed in dermatology literature, with reported concerns including unknown product purity, naevus darkening and systemic effects consistent with non-selective agonism [4,12].

Limitations of the current literature

• No controlled efficacy data for Melanotan II. The only human studies are small pilots; receptor-selectivity data come from heterologous expression systems [7,8,14].
• Selectivity values are assay-dependent. Binding affinities differ across radioligands and cell lines, so cross-study comparisons are approximate [7,8].
• Product identity in the informal market is unverified. Analyses of material sold as "melanotan" have raised purity and identity concerns, which limits the interpretability of anecdotal reports [4,12].
• Family-level terms are ambiguous. "Melanotan peptide" or "tanning peptide" may refer to either analogue; only the numeral or INN identifies the compound.

Where to source for research

Melanotan I and Melanotan II are listed by several research-chemical suppliers, typically as lyophilised powders in vials labelled by milligram content and by the notations catalogued above. Researchers evaluating suppliers should request a lot-specific certificate of analysis with HPLC purity and mass confirmation (about 1,646 g/mol for Melanotan I, 1,024 g/mol for Melanotan II), since the two are easily confused under abbreviated labels. Current research-grade availability includes Short Chain Aminos, BioPep, Catalyst Research and Apex Research Services. Our supplier evaluation guide and supplier reviews outline the documentation researchers can reasonably expect. All listings are for laboratory research use only.

Frequently asked questions

What is mt2?

"mt2" (also written mt-2, MT-II or melanotan-2) is the catalogue abbreviation for Melanotan II, a cyclic lactam heptapeptide analogue of α-MSH designed at the University of Arizona in 1989 [6]. It is a non-selective agonist at MC1R, MC3R, MC4R and MC5R [7,8]. The abbreviation should not be confused with MT-2, the metallothionein isoform.

What is the difference between mt1 and mt2?

mt1 (Melanotan I, afamelanotide) is a linear 13-residue peptide that retains the full α-MSH backbone with two substitutions and acts predominantly at MC1R [5,9]. mt2 (Melanotan II) is a truncated, cyclised heptapeptide that gained activity at MC3R, MC4R and MC5R [6,7]. Only Melanotan I is an approved medicine [9].

Are the melanotan peptides the same as bremelanotide (PT-141)?

No. Bremelanotide is a metabolite and close analogue of Melanotan II in which the C-terminal amide is replaced by a carboxylic acid; it favours MC4R and is approved for hypoactive sexual desire disorder [1,10]. Melanotan II itself has not completed controlled efficacy trials [14].

What does "tanning peptides" mean in a research catalogue?

It is an informal umbrella label for MC1R-active α-MSH analogues, grouped by their pigmentation pharmacology rather than by chemistry [4]. The peer-reviewed literature describes this pharmacology in porphyria trials and pilot studies [9,14]; the label is not a chemical class and carries no use recommendation.

Why does melanotan 2 reddit appear in search results for the compound?

Discussion forums host anecdotal threads about material sold as Melanotan II. Published analyses have raised concerns about the purity and identity of such material [4,12], so forum reports are not a substitute for the controlled studies cited here and are not a protocol source.

Does mt-ii peptide act only on the skin?

No. Because the cyclic scaffold engages MC3R, MC4R and MC5R in addition to MC1R, studies have reported central effects including appetite and erectile responses alongside pigmentation [7,14,15]. This non-selectivity is the reason MC4R-directed successors such as setmelanotide were engineered for receptor preference [11].

Which receptor mediates pigmentation for a melanotan peptide?

MC1R on melanocytes. Its activation raises cAMP, activates PKA/CREB and induces MITF and tyrosinase transcription, shifting melanin synthesis toward eumelanin [3,13]. This cascade is shared by α-MSH and both synthetic analogues [5,6].

Works Cited

1. 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. PMID 16412534.
2. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD. The cloning of a family of genes that encode the melanocortin receptors. Science. 1992;257(5074):1248–1251. doi:10.1126/science.1325670. PMID 1325670.
3. Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736–749. doi:10.1210/er.2006-0034. PMID 17077189.
4. Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol. 2017;56(10):975–980. doi:10.1111/ijd.13585.
5. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al. 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci USA. 1980;77(10):5754–5758. doi:10.1073/pnas.77.10.5754.
6. Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J Med Chem. 1989;32(12):2555–2561. PMID 2555512.
7. Schiöth HB, Muceniece R, Mutulis F, et al. Selectivity of cyclic [D-Nal7] and [D-Phe7] substituted MSH analogues for the melanocortin receptor subtypes. Peptides. 1997;18(7):1009–1013. PMID 9357059.
8. Hruby VJ, Lu D, Sharma SD, et al. Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J Med Chem. 1995;38(18):3454–3461. PMID 7658432.
9. Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48–59. doi:10.1056/NEJMoa1411481. PMID 26132941.
10. Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899–908. doi:10.1097/AOG.0000000000003500. PMID 31599840.
11. Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020;8(12):960–970. doi:10.1016/S2213-8587(20)30364-8. PMID 33137293.
12. Evans-Brown M, Dawson RT, Chandler M, McVeigh J. Use of melanotan I and II in the general population. BMJ. 2009;338:b566. doi:10.1136/bmj.b566. PMID 19224885.
13. D'Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci. 2013;14(6):12222–12248. doi:10.3390/ijms140612222. PMID 23749111.
14. 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 Sci. 1996;58(20):1777–1784. doi:10.1016/0024-3205(96)00160-9. PMID 8637402.
15. Wessells H, Fuciarelli K, Hansen J, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998;160(2):389–393. PMID 9679884.

All content strictly for research reference. Melanotan I, Melanotan II and the other melanocortin agonists discussed are research compounds in this context; they are not for human or veterinary use, and nothing in this article constitutes guidance on handling, administration or protocols. Related reviews: Melanotan II single-compound review · Melanotan I (afamelanotide) · PT-141 (bremelanotide) · 5-Amino-1MQ and the NNMT inhibitor family.