Melanotan I (Afamelanotide / NDP-α-MSH)
Also Known AsAfamelanotide · NDP-α-MSH · NDP-MSH · [Nle4,D-Phe7]-α-MSH · CUV1647 · Scenesse
Developed in the 1980s by Victor Hruby and Mac Hadley at the University of Arizona as a synthetic linear analog of α-melanocyte-stimulating hormone (α-MSH). The [Nle4,D-Phe7] substitutions confer enhanced potency and enzymatic stability compared to native α-MSH. Later developed by Clinuvel Pharmaceuticals as afamelanotide (Scenesse), receiving EMA approval in 2014 for erythropoietic protoporphyria (EPP).
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂How Melanotan I Works
MC1R Agonism
Melanotan I binds the melanocortin-1 receptor (MC1R) on melanocytes with high affinity, activating adenylyl cyclase and increasing intracellular cAMP. This triggers the MITF-mediated transcription of melanogenic enzymes (tyrosinase, TRP-1, TRP-2), leading to eumelanin synthesis and transfer to keratinocytes.
Eumelanin Pathway Shift
By activating MC1R signaling, Melanotan I shifts the melanogenesis ratio from pheomelanin (red/yellow, photosensitizing) toward eumelanin (brown/black, photoprotective). Eumelanin absorbs UV radiation and scavenges reactive oxygen species, providing intrinsic photoprotection independent of UV exposure.
Anti-inflammatory Melanocortin Signaling
Melanocortin receptor activation by α-MSH analogs suppresses NF-κB–mediated pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6) and upregulates anti-inflammatory mediators (IL-10). This pathway is independent of pigmentation and underlies the compound's immunomodulatory research interest.
DNA Damage Response Enhancement
MC1R signaling activates nucleotide excision repair (NER) pathways in UV-exposed melanocytes, independent of pigmentation. Research suggests α-MSH analogs enhance the repair of cyclobutane pyrimidine dimers (CPDs), a primary form of UV-induced DNA damage.
Published Research
Photoprotection & UV-Related Skin Damage
StrongPhase III clinical trials demonstrated that afamelanotide produces significant melanin density increases and reduces phototoxic reactions in patients with erythropoietic protoporphyria (EPP). Studies in healthy volunteers show increased melanin optical density and reduced sunburn response (increased minimal erythema dose) without UV exposure. EMA-approved for EPP since 2014.
Erythropoietic Protoporphyria (EPP)
StrongRandomized controlled trials across Europe demonstrated that subcutaneous afamelanotide implants significantly increased pain-free time in sunlight and reduced severity of phototoxic episodes in EPP patients. This led to regulatory approval (Scenesse) as an orphan drug in the EU, subsequently approved by the FDA in 2019.
DNA Repair & Melanoma Prevention
ModeratePreclinical studies demonstrate that MC1R activation enhances nucleotide excision repair of UV-induced DNA damage in melanocytes, independent of pigmentation. Research in MC1R-variant mouse models (analogous to red-haired individuals with impaired MC1R) shows that α-MSH analogs can rescue the DNA repair deficit, suggesting a potential role beyond simple pigmentation.
Anti-inflammatory Applications
PreclinicalThe melanocortin anti-inflammatory pathway (MC1R and MC3R activation suppressing NF-κB) has been studied in models of organ ischemia-reperfusion injury, inflammatory bowel disease, and neuroinflammation. α-MSH analogs reduce tissue injury in renal, hepatic, and cerebral ischemia models independent of pigmentary effects.
Vitiligo
ModeratePhase II studies combining narrowband UVB phototherapy with afamelanotide demonstrated accelerated and more extensive repigmentation in vitiligo patients compared to phototherapy alone. Melanocortin activation is hypothesized to stimulate melanocyte proliferation, migration, and melanogenesis in depigmented areas.
Safety Profile
Afamelanotide (Melanotan I) has a well-characterized safety profile from multiple Phase II/III clinical trials and post-marketing surveillance. The most common adverse effects are nausea, facial flushing, and headache, which are generally mild and transient. Darkening of pre-existing nevi has been observed but prospective dermatoscopic monitoring has not shown malignant transformation. Unlike Melanotan II, Melanotan I is a linear peptide with high MC1R selectivity and minimal MC3R/MC4R cross-reactivity, resulting in fewer off-target effects.
Handling & Storage
Reconstitute with bacteriostatic water. Direct gentle stream along vial wall — do not shake. Melanotan I is a linear peptide with moderate aqueous stability. Store reconstituted solution at 2-8°C and use within 21 days. Lyophilized powder stable at -20°C for 24+ months. Protect from light.
Peer-Reviewed Literature
- 1
Alpha-melanotropin: the minimal active sequence in the frog skin bioassay
Hruby VJ, Wilkes BC, Hadley ME, et al.
- 2
Afamelanotide for erythropoietic protoporphyria
Langendonk JG, Balwani M, Anderson KE, et al.
- 3
Melanocortins and the melanocortin 1 receptor: moving translationally towards melanoma prevention
Abdel-Malek ZA, Ruber A, Kadekaro AL, et al.
- 4
Pharmacokinetics and pharmacodynamics of afamelanotide and its clinical use in treating dermatologic disorders
Minder EI, Barman-Aksoezen J, Schneider-Yin X.
- 5
alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes
Kadekaro AL, Kavanagh R, Kanto H, et al.
Melanotan I FAQ
What is Melanotan I?
Melanotan I (afamelanotide) is a synthetic 13-amino-acid linear analog of α-melanocyte-stimulating hormone (α-MSH) developed at the University of Arizona. It features [Nle4,D-Phe7] substitutions that increase potency and enzymatic stability. It selectively activates the melanocortin-1 receptor (MC1R) to stimulate eumelanin production in melanocytes.
How does Melanotan I differ from Melanotan II?
Melanotan I is a linear 13-amino-acid peptide with high selectivity for MC1R. Melanotan II is a shorter, cyclic 7-amino-acid peptide that non-selectively activates MC1R, MC3R, MC4R, and MC5R. This broader receptor profile gives Melanotan II additional effects (appetite suppression, sexual arousal) but also more off-target side effects. Melanotan I has undergone formal clinical development and received regulatory approval (as Scenesse) while Melanotan II has not.
Is afamelanotide FDA approved?
Yes. Afamelanotide (brand name Scenesse) was approved by the EMA in 2014 and the FDA in October 2019 for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP). It is administered as a subcutaneous implant that releases the peptide over approximately 60 days.
How should Melanotan I be stored?
Lyophilized Melanotan I should be stored at -20°C for long-term stability (24+ months). Once reconstituted with bacteriostatic water, store at 2-8°C (refrigerator) and use within 21 days. Protect from light, as photodegradation can reduce potency.
What is the purity of G26x Peptides Melanotan I?
Our Melanotan I is 99%+ purity, independently verified by Janoshik Analytical with a full Certificate of Analysis (COA) available for each batch. It is supplied as a lyophilized powder manufactured under GMP-adjacent conditions.
Melanotan I Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
Melanotan I
10mgGet a deep, natural tan without the sun damage — stimulates your skin's own melanin production for photoprotection and a lasting bronze that doesn't fade.
- Develops a deep, natural-looking tan without UV damage
- Protects skin from sun damage and reduces burn risk
GLOW Blend
10-10-50mgThe beauty protocol — three peptides working together to tighten skin, build collagen, develop a natural glow, and burn facial fat for a sculpted, youthful appearance.
- All-in-one skin transformation — tighter, brighter, more radiant
- GHK-Cu for collagen + Melanotan I for glow + 5-Amino-1MQ for fat reduction
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.