Afamelanotide (Melanotan I)
Also known as: Melanotan I · MT-1 · CUV1647 · Scenesse · NDP-alpha-MSH
Contents
MW
1647.87 Da
Amino Acids
13 AA
Half-Life
15 hours (sustained from implant)
Route
Implant, SubQ
CAS
75921-69-6
Formula
C78H111N21O19
Amino Acid Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
Mechanism of Action
Afamelanotide (Melanotan I, [Nle4, D-Phe7]-α-MSH) is a 13-amino acid linear analog of α-MSH with a norleucine substitution at position 4 and D-phenylalanine at position 7 for enhanced MC1R selectivity and metabolic stability. FDA-approved as Scenesse.
MC1R SELECTIVITY: More selective for MC1R than Melanotan II — minimal MC3R/MC4R/MC5R activation. This means effective tanning/photoprotection WITHOUT the sexual arousal, appetite suppression, or nausea effects of MT-2.
MC1R → EUMELANIN: MC1R activation on melanocytes → adenylyl cyclase → cAMP → CREB → MITF transcription factor → tyrosinase and TRP-1/TRP-2 upregulation → eumelanin synthesis. Eumelanin is the photoprotective brown-black melanin (vs pheomelanin which is red-yellow and generates ROS upon UV exposure).
EPP APPLICATION: In erythropoietic protoporphyria (EPP), protoporphyrin IX accumulates in skin and causes severe phototoxic reactions upon light exposure. Eumelanin produced by afamelanotide absorbs UV and visible light, reducing protoporphyrin activation and enabling patients to tolerate sunlight.
Dosing Protocol
Low Dose
███ – ███ mcg/day
Standard Dose
███ mcg/day
High Dose
███ – ███ mcg/day
Dosing protocols are for paid members
Get exact dosing ranges, injection frequency, timing rationale, and reconstitution math.
Get Clinical Access — $79/moFrequency
Subcutaneous implant every 60 days (biodegradable rod).
Half-Life
15 hours (sustained from implant)
Reconstitution Guide
Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.
Unlock reconstitution guide →Clinical Warnings
FDA-approved only for EPP.
Mole darkening and new nevi — dermatologic monitoring required.
Melanoma screening before and during treatment.
Nausea, headache common.
Hyperpigmentation may be uneven.
Implant insertion requires clinical visit.
Contraindications
Absolute
Severe hepatic impairment
Pregnancy
Relative Cautions
Many moles/nevi
Melanoma history
Side Effect Profile
Mild
- ●Nausea
- ●Headache
- ●Flushing
Moderate
- ●Darkening of moles
- ●Skin discoloration
- ●Abdominal pain
Severe (Rare)
- ●Melanoma risk in predisposed individuals
Synergistic Peptides
Research Status
FDA APPROVED (Scenesse). PMID 26222094 (Langendonk 2015 NEJM): Phase III EPP trial — significant increase in pain-free sun exposure. Also EMA approved.
Frequently Asked Questions
How does Afamelanotide (Melanotan I) work?
Afamelanotide (Melanotan I, [Nle4, D-Phe7]-α-MSH) is a 13-amino acid linear analog of α-MSH with a norleucine substitution at position 4 and D-phenylalanine at position 7 for enhanced MC1R selectivity and metabolic stability. FDA-approved as Scenesse. MC1R SELECTIVITY: More selective for MC1R than Melanotan II — minimal MC3R/MC4R/MC5R activation. This means effective tanning/photoprotection WITHOUT the sexual arousal, appetite suppression, or nausea effects of MT-2. MC1R → EUMELANIN: MC1R acti
What is the standard dose of Afamelanotide (Melanotan I)?
Afamelanotide (Melanotan I) dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Subcutaneous implant every 60 days (biodegradable rod).
What is the half-life of Afamelanotide (Melanotan I)?
The half-life of Afamelanotide (Melanotan I) is 15 hours (sustained from implant). This determines optimal dosing frequency and timing.
Who should not use Afamelanotide (Melanotan I)?
Afamelanotide (Melanotan I) is absolutely contraindicated in: Severe hepatic impairment; Pregnancy. Use with caution in: Many moles/nevi; Melanoma history.
What are the side effects of Afamelanotide (Melanotan I)?
Common mild side effects include: Nausea, Headache, Flushing. Moderate effects: Darkening of moles, Skin discoloration, Abdominal pain.
What peptides stack well with Afamelanotide (Melanotan I)?
Afamelanotide (Melanotan I) is commonly stacked with: Melanotan II.
How do you reconstitute Afamelanotide (Melanotan I)?
Afamelanotide (Melanotan I) is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.
How long should you cycle Afamelanotide (Melanotan I)?
Afamelanotide (Melanotan I) cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.
References & Citations
10 PubMed studies · 3 clinical trials
New pharmacotherapies for the erythropoietic protoporphyrias: an analysis of trial protocols from a patient perspective.
Dechant Cornelia, Wäscher Sebastian, Granata Francesca, Gusset Nicole et al.. Orphanet journal of rare diseases. 2025
The erythropoietic protoporphyrias (EPP) are a group of ultra-rare (1:100.000) inborn errors of the heme biosynthesis characterised by painful phototoxic reactions in tissue exposed to visible light.
Letter to the Editor - Qualitative evidence submitted by patients to NICE: need for more quality or unrealistic and unfair requirements?
Falchetto Rocco, Barman-Aksözen Jasmin. Journal of comparative effectiveness research. 2025
Burden of illness and unmet needs in patients with erythropoietic protoporphyria and X-linked protoporphyria: A large US nationwide claims analysis.
DerSarkissian Maral, Norregaard Chelsea, Romdhani Hela, Muthukumar Aruna et al.. Journal of managed care & specialty pharmacy. 2025
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare genetic disorders caused by the accumulation of the toxic metabolite protoporphyrin IX, which results in painful phototox
Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.
Bardhan Mainak, Anand Ayush, Javed Amaan, Chilo Maria Andrea et al.. Diseases (Basel, Switzerland). 2025
Melanocortin receptors (MCRs) are responsible for various functions ranging from skin pigmentation, regulation of appetite, stress response and cognition, steroid synthesis, and energy balance to cell
Erythropoietic protoporphyria in childhood: clinical clues, missed diagnoses and emerging therapy.
Toenne Moritz, Schaefer Tim. European journal of pediatrics. 2025
Erythropoietic protoporphyria (EPP) is a rare photodermatosis presenting in early childhood with severe pain upon exposure to visible light, including sunlight and artificial sources, often without vi
Afamelanotide in managing cutaneous phototoxicity in erythropoietic protoporphyria: a Scottish perspective.
Dawe Robert S, Kerr Alastair, Eadie Ewan, Waterston Suzanne et al.. Clinical and experimental dermatology. 2025
German Cohort Observational Study to Investigate the Short- and Long-Term Safety and Clinical Effectiveness of Afamelanotide 16 mg (SCENESSE) in Patients With Erythropoietic Protoporphyria (EPP).
Homey Bernhard, Schelonke Kathrin, Schlegel Carla Marie, Bruch-Gerharz Daniela et al.. Photodermatology, photoimmunology & photomedicine. 2025
Afamelanotide 16 mg (SCENESSE) is the first approved treatment for erythropoietic protoporphyria (EPP). EPP is a rare autosomal recessive inherited disorder of the haem biosynthesis pathway, wh
Discovery of MT-7117 (Dersimelagon Phosphoric Acid): A Novel, Potent, Selective, and Nonpeptidic Orally Available Melanocortin 1 Receptor Agonist.
Sato Atsushi, Morokuma Kenji, Adachi Takashi, Andou Junki et al.. Journal of medicinal chemistry. 2024
Activation of the melanocortin 1 receptor (MC1R) mediates melanogenesis in melanocytes, anti-inflammatory effects in inflammatory cells, and antifibrotic effects in fibroblasts. Thus, MC1R agonists ar
Registered Clinical Trials
Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental Vitiligo
A Study to Assess the Changes in Pigmentation and Safety of Afamelanotide in Patients With Vitiligo on the Face
Implant Pharmacokinetic and Pharmacodynamic Study
Symptom Indications
Full Clinical Access
Complete Afamelanotide (Melanotan I) Protocol
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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.