Melanotan I (afamelanotide)

Overview

Melanotan I, whose international name is afamelanotide, is a synthetic analogue of alpha-MSH — the endogenous hormone that drives production of the pigment melanin. Two modifications (Nle at position 4, D-Phe at position 7) make it more stable and longer-acting than the natural hormone.

It is the linear counterpart of the already-present Melanotan II (which is cyclic and shorter) — chemically and pharmacologically distinct, but on the same melanocortin route. Melanotan I is also an approved medicine: under the name Scenesse it is used for photoprotection in erythropoietic protoporphyria (EPP), a rare condition with extreme light sensitivity.

That regulatory status is a fact about the respective authorities. At Peptalis, Melanotan I is available strictly for research use only — in-vitro, not for human or animal use.

Mechanism of action

Melanotan I activates the melanocortin-1 receptor (MC1R) on pigment cells, stimulating eumelanin synthesis and thereby providing photoprotection.

MC1R activation and pigment

• Melanotan I binds the melanocortin-1 receptor (MC1R) on melanocytes and drives production of eumelanin — the dark pigment form that absorbs UV light.
• This produces photoprotection, which is the basis of the approved use in EPP (Langendonk 2015).

Distinction from Melanotan II

• Melanotan I is a linear 13-aa peptide ([Nle4,D-Phe7]-alpha-MSH); Melanotan II is a cyclic 7-aa peptide with a broader melanocortin-receptor profile.
• Both engage the melanocortin route but differ in structure, selectivity and regulatory status.

Research findings

• Human (phase 3, RCTs): afamelanotide for erythropoietic protoporphyria (Langendonk 2015, NEJM)
• Mechanism/review: synthetic alpha-MSH analogue, MC1R-mediated photoprotection (Wu 2021)
• Mechanism context: MC1R/alpha-MSH as a melanogenesis stimulator (Fontanellas 2019)

Mechanism

• Melanotan I is an MC1R agonist that stimulates eumelanin synthesis and photoprotection; the mechanism is well described (Wu 2021; Fontanellas 2019).

Human studies

• Two pivotal phase 3, randomized, double-blind, placebo-controlled trials showed the effect of afamelanotide in erythropoietic protoporphyria; this formed the basis for approval (Langendonk 2015). Additional RCT evidence exists in, among others, polymorphic light eruption.

Research context

This profile describes what has been done and found in research. Regulatory and clinical facts are facts about the respective trials and authorities, not claims about a Peptalis product; the compound is for in-vitro laboratory research only (RUO).

Open questions

• The approved use concerns a rare condition (EPP); broader dermatological applications are still under study.
• Long-term safety data over many years are still being gathered.
• Direct comparison with Melanotan II in terms of selectivity and effect is limited to indirect data.

Research outlook

Melanotan I is a well-characterized, approved reference molecule for the melanocortin route (MC1R).

Alongside Melanotan II it makes the melanocortin family within the database internally comparable: linear/approved next to cyclic.

Scientific interest

Approved MC1R agonist (Scenesse) — a strong fact-about-the-regulator.

A comparison neighbour of Melanotan II on the melanocortin route.

A clear, photoprotective mechanism with phase 3 support.

Specifications

References

1. Afamelanotide for Erythropoietic Protoporphyria · Langendonk JG, et al. · N Engl J Med · 2015
2. Current and innovative emerging therapies for porphyrias with hepatic involvement · Fontanellas A, et al. · J Hepatol · 2019
3. Afamelanotide: An Orphan Drug with Potential for Broad Dermatologic Applications · Wu J, Cotliar R · J Drugs Dermatol · 2021

Availability

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