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Compound monograph

Melanotan II

Melanotan II is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone, closed by a lactam bridge between an aspartate and a lysine side chain.

Published: 2026-09-13Last updated: 2026-10-15Literature/identifier verification: 2026-08-23
Also known asMelanotan-IIMT-IIMT-2
Cyclic melanocortin analogs

01

Identity & nomenclature

Melanotan II is a synthetic cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone, closed by a lactam bridge between an aspartate and a lysine side chain.

The unqualified word melanotan is not a usable identity field. Melanotan II is this cyclic lactam analog; Melanotan I is afamelanotide, a linear thirteen-residue peptide with a different formula and mass. They are distinct molecules and are never interchangeable as identities — but neither are they unrelated: both are analogs of alpha-melanocyte-stimulating hormone and both belong to the melanocortin family. What differs is the structure.

Declared aliases and development codes: Melanotan-II, MT-II, MT-2.

02

Molecular properties

Molecular formulaC50H69N15O9
Molecular mass1024.18 Da
CAS Registry Number121062-08-6
PubChem CID92432
UNIIUPF5CJ93X7
Three-letter sequenceNle–Asp–His–D-Phe–Arg–Trp–Lys
Terminal groupsN-terminal acetylation; C-terminal amide

A linear one-letter string cannot describe this molecule and none is published here. The peptide is seven residues, closed into a ring by a lactam bridge between the aspartate side-chain carboxyl and the lysine side-chain amine; the N-terminal norleucine sits OUTSIDE that ring, so the cyclized portion spans six residues. Al-Obeidi et al. (PMID 2555512) describe the lactam as joining Asp5 and Lys10 in alpha-MSH numbering, which are Asp2 and Lys7 of this seven-residue chain. It also carries a D-phenylalanine. Written as a plain seven-residue sequence it would denote a different, linear compound.

03

Structural characteristics

Structure-activity work on the lactam scaffold reports that replacing the phenylalanine or the tryptophan with alanine abolished measurable activity at human MC3, MC4 and MC5 receptors, while replacing the histidine did not, and that substituting the arginine reduced potency roughly a hundredfold. Retro, enantio and retro-enantio analogs all lost substantial potency, which the source literature attributes primarily to side-chain topology rather than backbone arrangement. Separate work replacing the lactam cyclization with xylene-derived thioether linkers reports that the linker chemistry itself correlates with receptor affinity, indicating the ring is a determinant of the pharmacology rather than a passive constraint.

  • Side-chain to side-chain lactam bridge, Asp to Lys
  • Norleucine substitution
  • D-phenylalanine substitution

Ring closures: covalent bonds between residues, by position counted from the first residue of the chain.

  • Side-chain lactam Asp2–Lys7: side-chain carboxyl (Cγ) to side-chain ε-amino nitrogen (Nζ). Source numbering: Asp5–Lys10 in alpha-MSH numbering. Source: PMID 2555512.

Terminal features: N-terminal acetylation, C-terminal amide.

04

Molecular targets & mechanisms

Melanocortin receptors

MC1R · MC2R · MC3R · MC4R · MC5R · MCR

A family of five G protein-coupled receptors, MC1R through MC5R. ACTH recognition and signaling at MC2R depend on the accessory protein MRAP. Native hormones, peptide analogs and nonpeptide ligands differ in receptor-subtype recognition and functional direction; binding affinity, agonism and antagonism must be interpreted separately in the experimental system studied.

05

Analytical considerations

The identity question specific to this compound is its relationship to PT-141, which differs only in that the C-terminal amide is a free acid. The calculated neutral monoisotopic masses are 1023.54027 for Melanotan II and 1024.52428 for PT-141, a difference of 0.98402 Da; the average masses are 1024.18 and 1025.17. These are calculated neutral values, not measured mass-to-charge ratios, and an observed ion will differ from them by the charge carriers it picked up. A well-specified measurement separates the two compounds without difficulty. The trap is a measurement that is not well specified, and it has a particular shape here: the first carbon-13 isotope peak of Melanotan II falls at 1024.54363, within 0.0194 Da of PT-141's monoisotopic value. A check that asks only whether a signal appears near 1024.5 is therefore satisfied by either compound, and resolving those two specific peaks needs a resolving power on the order of 53,000 at that mass — a figure that describes the scale of the separation required, not a guarantee of baseline resolution, reliable detection of a minor component, or identification on its own. Practically: a certificate reporting a single rounded mass alongside an HPLC purity figure has not established which of the two is present, and neither has a chromatographic method that was never shown to separate them.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • Macrophage cultures

    Getting et al. reported that MTII inhibited KC and interleukin-1beta release in macrophage cultures.

    Reference [4]

  • Macrophage cultures

    Getting et al. observed increased cAMP accumulation in macrophage cultures exposed to MTII, and the increase was attenuated by SHU9119.

    Reference [4]

Animal studies

  • Mouse crystal-induced peritonitis model

    Getting et al. reported a significant reduction in polymorphonuclear leukocyte accumulation in the peritoneal cavity of mice in a crystal-induced peritonitis model that included MTII.

    Reference [4]

06

Verified bibliography

Cited studies by type

The 5 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    Structure-function studies on the cyclic peptide MT-II, lactam derivative of alpha-melanotropin.

    Bednarek MA, Silva MV, Arison B, MacNeil T, Kalyani RN, Huang RR, Weinberg DH

    Peptides · 1999 · Journal Article

    current
    PMID 10447101DOI 10.1016/s0196-9781(99)00048-0Melanotan IIMC1R

  2. Reference 2

    CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists.

    Tomassi S, Dimmito MP, Cai M, D'Aniello A, Del Bene A, Messere A, Liu Z, Zhu T, Hruby VJ, Stefanucci A, Cosconati S, Mollica A, Di Maro S

    Journal of medicinal chemistry · 2022-02-21 · Journal Article

    current
    PMID 35188390DOI 10.1021/acs.jmedchem.1c01848Melanotan IIMC1R

  3. Reference 3

    Goldilocks-Inspired Design of Mid-Size Macrocycles for Selective Targeting of Human Melanocortin Receptors.

    Merlino F, Jia L, Boccino I, Carotenuto A, Tammaro F, Santoro F, Thompson PE, Grieco P

    Journal of medicinal chemistry · 2026-08-13 · Journal Article

    current
    PMID 42340853PMC13492293DOI 10.1021/acs.jmedchem.6c01074Melanotan IIPT-141 (Bremelanotide)MC1R

  4. Reference 4

    Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides.

    Getting SJ, Schiöth HB, Perretti M

    The Journal of pharmacology and experimental therapeutics · 2003-05-15 · Journal Article

    current
    PMID 12750433DOI 10.1124/jpet.103.051623alpha-MSHSHU9119KPVMelanotan IIMC1R

  5. Reference 5

    Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics.

    Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ

    Journal of medicinal chemistry · 1989-12 · Journal Article

    current
    PMID 2555512DOI 10.1021/jm00132a010Melanotan II

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Bednarek MA et al. 1999Study models reported: in vitro · from the abstract
Tomassi S et al. 2022Study models reported: in vitro · from the abstract
Merlino F et al. 2026Study models reported: in vitro · from the abstract
Getting SJ et al. 2003Study models reported: in vitro; animal (mouse) · from the abstract
Al-Obeidi F et al. 1989Study models reported: in vitro · from the abstract

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Catalog listing

Record history

Published 2026-09-13.

  • : Sequence and structure
  • : Sequence and structure, References
  • : Identity and nomenclature, Sequence and structure, Analytical notes
  • : References

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. Melanotan II. Published 2026-09-13; updated 2026-10-15. https://purelypeptides.org/research/compounds/melanotan-ii/

10

Methodology & citation verification

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