Melanotan 1 (10 mg)

Research-grade α-MSH analog / selective MC1R agonist

Melanotan 1 (MT-1) — also known as Afamelanotide, NDP-α-MSH, or [Nle⁴-D-Phe⁷]-α-MSH — is a synthetic linear 13-amino acid peptide engineered from the endogenous melanocortin hormone α-melanocyte-stimulating hormone (α-MSH). It contains two stabilizing amino-acid substitutions (Norleucine⁴ and D-Phenylalanine⁷), which significantly enhance its melanogenic potency, receptor selectivity, and metabolic stability.

Melanotan 1 is a highly selective MC1R agonist, unlike Melanotan 2 (which activates MC1R, MC3R, MC4R and MC5R). Because of this selectivity, MT-1 is studied primarily for melanogenesis, DNA photoprotection, oxidative-stress resistance, pigmentation disorders, and phototoxicity research, avoiding the off-target sexual and behavioral effects associated with MT-II.

Afamelanotide (Melanotan 1) is approved only in specific regions for erythropoietic protoporphyria (EPP) photoprotection but remains research-only in most jurisdictions.

Specifications

Synonyms: Melanotan 1, MT-1, Afamelanotide, NDP-α-MSH, [Nle⁴-D-Phe⁷]-α-MSH
Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂
Molecular Formula: C₇₈H₁₁₁N₂₁O₁₉
Molecular Weight: ~1646.9 g/mol
Class: Synthetic melanocortin-1 receptor (MC1R) agonist / α-MSH analog
Presentation: Lyophilized powder, 10 mg per vial (research purity ≥98%)

Mechanism of Action and Melanocortin Pathways

Melanotan 1 selectively activates the MC1R receptor on melanocytes:

1. MC1R activation → cAMP increase → melanin synthesis

Binding of MT-1 to MC1R increases intracellular cAMP, leading to:

• Upregulation of tyrosinase

• Increased eumelanin synthesis

• Enhanced melanosome distribution

• Darker pigmentation with stronger photoprotective properties

2. DNA photoprotection and oxidative stress resistance

β-eumelanin produced via MC1R activation:

• Exhibits strong UV-absorbing and antioxidant properties

• Reduces UV-induced DNA photolesions (e.g., CPDs, 6-4 photoproducts)

• Enhances keratinocyte and melanocyte survival in UV-stress models

3. Anti-inflammatory and immunomodulatory effects

MC1R activation also influences:

• Downregulation of NF-κB inflammatory pathways

• Reduction of pro-inflammatory cytokines in UV-exposed tissue

• Enhanced cutaneous barrier and repair responses

4. No MC4R activation → no sexual side effects

Unlike Melanotan 2, MT-1 does not significantly activate MC3R/MC4R; therefore it:

• Does not induce pro-erectile or libido-related CNS effects

• Avoids the sympathomimetic and behavioral effects associated with MT-II

Pigmentation Research and Photoprotection

UV-Protection and DNA Repair Studies

Research demonstrates that MT-1–induced eumelanin:

• Strengthens natural photoprotection

• Decreases UV-generated cyclobutane pyrimidine dimers (CPDs)

• Reduces oxidative DNA damage

• Improves keratinocyte survival following UV challenge

Pigmentation disorders

MT-1 has been studied in:

• Erythropoietic protoporphyria (EPP) – increased light tolerance

• Vitiligo – repigmentation when combined with UV therapy

• Photodermatoses – reduction in photosensitivity markers

Because of its selectivity, MT-1 is considered the cleanest pharmacological tool for studying melanin biology without CNS interference.

Systemic and Dermatologic Research Applications

1. Oxidative stress modulation

MC1R agonism increases antioxidant defenses:

• Enhancement of superoxide dismutase activity

• Reduced ROS accumulation in UV-challenged cells

• Improved cell survival under oxidative stress

2. Immunomodulation

MT-1 reduces inflammatory mediator release:

• TNF-α

• IL-1β

• IL-6

• COX-2 pathway mediators

3. Pain, phototoxicity and porphyria models

Because eumelanin shields phototoxic molecules from UV activation, MT-1 is widely used to study:

• Phototoxicity attenuation

• Porphyrin-related photoreaction mechanisms

• Behavioral light-avoidance models

4. Cosmetic and pigmentation science

In vitro research uses MT-1 to model:

• Controlled melanogenesis pathways

• UV-resistant pigmentation

• Melanosome transport biology

Safety, Limitations and Regulatory Status

Approved only in limited contexts

Afamelanotide (MT-1) is approved in the EU, USA, and Australia only for EPP under specialist supervision. Outside this, MT-1 exists strictly as a research compound.

Research-reported adverse effects

From clinical and experimental data:

• Mild nausea

• Hyperpigmentation (focal or diffuse)

• Increased appearance of nevi (requires monitoring in clinical contexts)

• Occasional flushing or fatigue

Key distinctions from Melanotan 2

MT-1:

• Has no documented libido-modulating effects

• Possesses a longer-lasting and cleaner MC1R profile

• Is considered pharmacologically more predictable for pigmentation studies

Research Use Only – Important Notice

This Melanotan 1 (10 mg) product is supplied exclusively for laboratory research.

• Not for human or veterinary use

• Not for tanning, cosmetic, therapeutic, or diagnostic applications

• Intended only for in vitro testing or controlled animal studies

• All descriptions summarize preclinical and mechanistic findings

• Not to be interpreted as medical or dosing guidance

References (Non-Wikipedia, with Links)

1. Dorr RT et al. Pharmacologic characterization of afamelanotide, a novel melanocortin agonist.
   https://pubmed.ncbi.nlm.nih.gov/16135082/

• Kadekaro AL et al. Alpha-MSH and MC1R regulate DNA repair and melanocyte survival.
  https://pubmed.ncbi.nlm.nih.gov/17551931/

Abdel-Malek Z et al. MC1R polymorphisms, UV response, and melanogenesis.
https://pubmed.ncbi.nlm.nih.gov/22170499/

Langendonk JG et al. Afamelanotide therapy in erythropoietic protoporphyria.
https://pubmed.ncbi.nlm.nih.gov/26291367/

Delphi/Scenesse safety and clinical documentation (Afamelanotide regulatory dossier).
https://www.clinuvel.com/

Wong TH et al. MC1R agonists and photoprotection research.
https://pubmed.ncbi.nlm.nih.gov/29704977/

Busca R & Ballotti R. Cyclic AMP and melanogenesis pathways.
https://pubmed.ncbi.nlm.nih.gov/15250929/

Eves PC et al. MC1R activation reduces UV-induced oxidative DNA damage.
https://pubmed.ncbi.nlm.nih.gov/15908788/