Afamelanotide
Afamelanotide is a synthetic 13-amino-acid analogue of α-melanocyte-stimulating hormone, [Nle4, D-Phe7]-α-MSH, that activates the melanocortin 1 receptor. It is FDA-approved as Scenesse (2019) for erythropoietic protoporphyria.
Overview
Afamelanotide is a linear analogue of α-melanocyte-stimulating hormone (α-MSH), the peptide that stimulates melanin production in skin. Researchers at the University of Arizona showed in the 1980s that replacing methionine 4 with norleucine and L-phenylalanine 7 with D-phenylalanine produced an analogue far more potent and longer-lasting than native α-MSH. Known in research as NDP-α-MSH and earlier as melanotan I, it was later developed as a pharmaceutical under the name afamelanotide.
Afamelanotide is the first approved drug acting on the melanocortin 1 receptor (MC1R). It is marketed as Scenesse, a subcutaneous implant, and was approved by the FDA in 2019 to increase pain-free light exposure in adults with erythropoietic protoporphyria, a rare genetic disorder causing severe phototoxic pain. It is also authorized in the European Union for this condition. It should not be confused with melanotan II, a different, cyclic and less receptor-selective analogue that is not approved.
Compare: Afamelanotide vs Melanotan II.
Structure
Afamelanotide is a 13-residue linear peptide with the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It shares the length and N-acetyl, C-amide termini of native α-MSH but carries two substitutions: norleucine at position 4, which removes the oxidation-prone methionine, and D-phenylalanine at position 7, which increases potency and resistance to enzymatic degradation. The core His-D-Phe-Arg-Trp motif is the pharmacophore shared with other melanocortin agonists. Research material is usually supplied as an acetate or TFA salt.
Mechanism
Afamelanotide is a potent agonist of MC1R, a Gs-coupled receptor on melanocytes. Receptor activation raises intracellular cyclic AMP and promotes synthesis of eumelanin, the darker, more photoprotective form of melanin, increasing skin pigmentation independent of ultraviolet exposure. In erythropoietic protoporphyria, the proposed benefit is that increased eumelanin reduces the amount of visible light reaching protoporphyrin in dermal vessels. NDP-α-MSH also activates other melanocortin receptors in vitro, though its pharmaceutical use is centered on MC1R.
Research
Erythropoietic protoporphyria
Randomized, placebo-controlled trials in the United States and Europe evaluated afamelanotide implants in adults with erythropoietic protoporphyria, measuring time spent in direct sunlight without pain and related quality-of-life outcomes. Results from these phase 3 studies supported regulatory approval in the European Union and, in 2019, by the FDA. The trials were relatively small, reflecting the rarity of the disease, and outcome measures were tailored to the condition's light-triggered symptoms.
Other photodermatoses and vitiligo
Afamelanotide has been studied in other conditions where pigmentation or photoprotection may matter, including polymorphic light eruption and vitiligo, the latter in combination with narrowband ultraviolet B phototherapy. These studies reported pigmentation changes in some participants, but they are smaller or earlier-stage than the protoporphyria program, and afamelanotide is not approved for these uses. Regulatory approval has been limited to erythropoietic protoporphyria, and the other indications remain investigational.
Melanocortin research tool
As NDP-α-MSH, the peptide has long been a standard high-affinity ligand in melanocortin receptor pharmacology, used in radioligand binding assays and as a reference agonist in studies of MC1R, MC3R, MC4R and MC5R. This use predates its clinical development and accounts for a large share of the published literature mentioning the compound. Its high affinity and stability made it more convenient than native α-MSH for such assays, and labeled versions have been used to map receptor distribution in tissues.
Safety considerations
Because afamelanotide increases pigmentation, darkening of existing nevi and skin is an expected effect, and clinical programs monitored skin lesions. Approved labeling also describes administration restrictions and adverse effects observed in trials. Interest in the long-term dermatological effects of melanocortin agonists continues, particularly given widespread unregulated use of related tanning peptides, which have different properties and have not undergone comparable evaluation.
Regulatory status
Afamelanotide is FDA-approved as Scenesse (2019) to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria, as a subcutaneous implant administered by trained health professionals. It is also authorized in the European Union for this condition. It is not approved for cosmetic tanning or other uses. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page, and report HPLC purity with the chromatogram. A key distinction is from native α-MSH and from melanotan II: native α-MSH contains methionine 4 and L-Phe7, giving a different mass, while melanotan II is a shorter cyclic lactam. The HPLC method should resolve the L-Phe7 diastereomer, which has the same mass. Tryptophan oxidation and deamidation or truncation products should be reported, and the counter-ion and net peptide content stated.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized afamelanotide sealed at -20 °C or colder, protected from light and moisture, and allow vials to reach room temperature before opening. The norleucine substitution removes the methionine oxidation risk present in native α-MSH, but the tryptophan residue remains light- and oxidation-sensitive. Prepare solutions for lab use in sterile water or buffer, keep them refrigerated for short-term use, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles.
Download the Afamelanotide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Afamelanotide in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is afamelanotide the same as melanotan II?
No. Afamelanotide, also called melanotan I or NDP-α-MSH, is a linear 13-residue analogue of α-MSH. Melanotan II is a shorter cyclic lactam peptide that activates several melanocortin receptors more broadly. Afamelanotide is FDA-approved for erythropoietic protoporphyria, whereas melanotan II is not approved for any use.
Is afamelanotide FDA approved?
Yes. Afamelanotide was approved by the FDA in 2019 as Scenesse, a subcutaneous implant, to increase pain-free light exposure in adults with erythropoietic protoporphyria. It is also authorized in the European Union. It is not approved for cosmetic tanning. Treatment is given by trained health professionals.
How does afamelanotide increase pigmentation?
Afamelanotide activates the melanocortin 1 receptor on melanocytes, raising cyclic AMP and stimulating production of eumelanin, the dark, photoprotective pigment. This happens without the need for ultraviolet exposure, which is why it was studied in light-sensitive disorders. The response is a pigmentary change and does not remove the need for other sun-protection measures in research subjects.
Related compounds
- Melanotan II
Melanotan II is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone that activates several melanocortin receptors. It is not approved as a medicine anywhere, and regulators have warned about unlicensed tanning products.
- PT-141 (bremelanotide)
PT-141, or bremelanotide, is a cyclic heptapeptide melanocortin receptor agonist derived from melanotan II. It was FDA-approved in 2019 as Vyleesi for hypoactive sexual desire disorder in premenopausal women.
- Setmelanotide
Setmelanotide is a synthetic cyclic eight-amino-acid melanocortin 4 receptor (MC4R) agonist. It is FDA-approved as Imcivree (2020) for chronic weight management in certain rare genetic forms of obesity affecting the leptin-melanocortin pathway.
References
- PubMed: all indexed literature on Afamelanotide
- ClinicalTrials.gov: registered studies mentioning Afamelanotide
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