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Aesthetic

MT-1

Also known as: Melanotan-1, Melanotan I, Afamelanotide, Scenesse, CUV1647, α-MSH analogue

Afamelanotide (MT-1) is a synthetic MC1R-selective alpha-MSH analogue that stimulates eumelanin production, approved as Scenesse for erythropoietic protoporphyria (EPP) and...

Last updated July 11, 2026

Overview

MT-1 — also known as Melanotan-1 and afamelanotide — is a synthetic 13-amino-acid analogue of naturally occurring alpha-melanocyte-stimulating hormone (α-MSH). It was developed as a more stable, longer-acting derivative designed to activate melanocortin receptors and drive melanin synthesis in the skin. Unlike alpha-MSH itself, which has a plasma half-life of only a few minutes, afamelanotide is metabolically resistant to rapid enzymatic degradation. The compound achieved regulatory approval under the brand name Scenesse (Clinuvel Pharmaceuticals) — first in Italy and Switzerland (2010), then across the European Union via EMA approval (January 2015), and finally in the United States (FDA, October 2019). All approvals are for a single indication: reducing phototoxic pain in adults with erythropoietic protoporphyria (EPP), a rare inherited disorder in which accumulated protoporphyrin IX causes severe burning pain on light exposure. The approved formulation is a controlled-release subcutaneous implant delivering 16 mg afamelanotide over approximately 60 days. MT-1 is meaningfully different from Melanotan II (MT-2). MT-1 is highly selective for MC1R, the receptor found on melanocytes, and does not substantially activate MC3R or MC4R — the receptors responsible for MT-2's libido effects, spontaneous erections, nausea, and appetite suppression. This selectivity makes MT-1's side-effect profile substantially cleaner in clinical trials, with nausea and headache as the most common events, but without the sexualised and appetite-related effects associated with MT-2. Beyond EPP, afamelanotide has been investigated in Phase II trials for polymorphous light eruption, solar urticaria, actinic keratosis prevention in organ-transplant recipients, vitiligo, and acne vulgaris. Results in polymorphous light eruption showed promise, but phase III trials for most indications outside EPP have not followed. In the research and fitness community, injectable MT-1 (lyophilised powder reconstituted with bacteriostatic water) is used off-label for cosmetic tanning. This is unregulated, unapproved use. Research-use material is not subject to the manufacturing quality controls that govern Scenesse implants.

How it works

Afamelanotide acts as a potent agonist at the Melanocortin 1 Receptor (MC1R) on melanocytes in the skin. MC1R is a G-protein-coupled receptor: agonist binding activates adenylyl cyclase via Gs, raising intracellular cyclic AMP (cAMP), which activates protein kinase A (PKA). PKA in turn phosphorylates and activates MITF (microphthalmia-associated transcription factor), the master regulator of melanogenesis. MITF upregulates tyrosinase and related enzymes (TRP-1, TRP-2) that catalyse the conversion of tyrosine through DOPA and dopaquinone to eumelanin — the dark-brown/black pigment that absorbs and scatters UV radiation, reducing DNA photodamage to keratinocytes. Critically, afamelanotide stimulates eumelanin (as opposed to phaeomelanin, the red-yellow pigment linked to higher UV sensitivity and oxidative stress). Eumelanin provides superior photoprotection and also scavenges reactive oxygen species, suppresses UV-induced inflammation, and promotes DNA repair pathways — mechanisms that are directly relevant to its therapeutic benefit in EPP. MT-1's selectivity for MC1R over MC3R and MC4R is a key pharmacological distinction from Melanotan II. Because MC4R activation drives libido, sexual arousal, and appetite suppression, MT-1's receptor profile avoids these off-target effects in therapeutic doses. The amino-acid substitution of D-phenylalanine at position 7 of the alpha-MSH sequence confers metabolic stability and extended receptor binding without markedly broadening receptor selectivity.

Researched effects

  • Clinical Increases pain-free light exposure time in adults with erythropoietic protoporphyria (EPP)
  • Clinical Reduces the number of phototoxic reactions in EPP patients
  • Clinical Improves quality of life in EPP patients (documented via validated QoL scores)
  • Clinical Reduces symptoms of polymorphous light eruption with short-term photoprotection
  • Clinical Stimulates eumelanin-based skin tanning in the absence of UV exposure
  • Clinical May reduce phototoxic liver damage associated with EPP
  • Preclinical Potential protection against actinic keratosis in high-risk organ-transplant recipients
  • Anecdotal Cosmetic skin darkening for aesthetic tanning purposes in healthy individuals

Evidence levels: Clinical (human trials) · Preclinical (animal/lab) · Anecdotal (community-reported).

Dosing reference

For research reference only — not a recommendation.

Clinical / studied dosing

The only FDA- and EMA-approved dosing regimen for afamelanotide is Scenesse: a single 16 mg subcutaneous controlled-release implant inserted above the anterior supra-iliac crest every 60 days by a trained healthcare provider. Treatment is initiated approximately 60 days before the expected period of increased sun exposure and continued throughout the high-risk season. Clinical trials used 3–5 implants per year depending on trial duration. In the pivotal Phase III trials (NEJM, 2015), 168 patients across EU and US cohorts received this regimen; efficacy was demonstrated by significantly increased hours of pain-free sun exposure vs. placebo (median 69.4 h vs. 40.8 h in the US trial, p=0.04). There is no approved injectable formulation. The implant is prescription-only and administered in clinic settings.

Community-reported dosing (anecdotal)

Anecdotal and research-reference only; not medical advice, not a recommended protocol, and not a substitute for medical consultation. Community sources describe injectable MT-1 (lyophilised powder reconstituted with bacteriostatic water) administered subcutaneously. Commonly cited starting doses are 250 mcg (0.25 mg) once or twice per week, with some sources describing escalation to 500 mcg per dose. Protocols are typically framed as 6–12 week cycles coinciding with intended sun exposure periods. Some sources cite a Monday/Thursday twice-weekly schedule drawn from a 10 mg vial reconstituted with 2 mL bacteriostatic water (yielding 500 mcg/0.1 mL). These figures are extrapolated from clinical pharmacology and community practice — they have not been validated in a controlled human trial for cosmetic use, carry uncertain safety implications in healthy populations, and use unregulated research-grade material of unknown purity.
Half-life
Afamelanotide has a short plasma half-life of approximately 30 minutes after systemic exposure. When delivered via the approved subcutaneous implant (Scenesse), release kinetics are substantially different: the majority of drug is released within the first two days, with approximately 90% released by day 5 and plasma levels undetectable by day 10. The implant therefore provides an acute pharmacological pulse rather than sustained steady-state exposure. After subcutaneous injection of reconstituted powder (research form), pharmacokinetics would more closely approximate the short 30-minute half-life, requiring more frequent dosing to maintain biological effect.
Routes
subcutaneous implant (approved Scenesse formulation), subcutaneous injection (research peptide form)

Safety & side effects

Approval status: Afamelanotide (Scenesse) is FDA-approved (October 2019) and EMA-approved (January 2015) exclusively for erythropoietic protoporphyria in adults. This approval covers only the 16 mg controlled-release subcutaneous implant administered by a clinician — it does not extend to injectable research-grade material or off-label cosmetic use. Melanoma risk: No evidence from Phase III clinical trials or the long-term observational study (115 patients, up to 8 years, 1,023 implants) demonstrates that afamelanotide causes or accelerates melanoma. Eumelanin, which MT-1 stimulates, is photoprotective and has antioxidant properties; this differs from phaeomelanin, which is associated with UV-induced oxidative stress. One melanoma case was reported during trials in a patient with pre-existing dysplastic nevi and heavy prior UV exposure; investigators concluded it was unrelated to the study drug. Nevertheless, the EMA required a post-approval safety study (PASS) monitoring for melanoma and nevi changes; as of available data, no melanoma attributable to afamelanotide has been reported. As a precaution, patients with personal or family history of melanoma or numerous dysplastic nevi should be counselled carefully and monitored. Documented side effects (from Phase III and long-term studies): nausea (most common, typically resolving within 72 hours of implant insertion), headache, implant-site hyperpigmentation, fatigue, dizziness, and flushing. No serious adverse events were attributed to the study drug in Phase III trials. Contraindications include liver or kidney impairment, age under 17 or over 70 years, pregnancy, and breastfeeding. Research-use material: Injectable MT-1 sold as a research peptide is unregulated. It is not manufactured to pharmaceutical GMP standards, may be impure, mislabelled, or contaminated, and has no quality assurance equivalent to the approved implant. Human use of research-grade material carries inherent product-quality risks above any pharmacological risk profile from clinical data. WADA: Afamelanotide and related melanocortin peptides are prohibited in competitive sport under the WADA Prohibited List (Peptide Hormones and Related Substances, Section S2). Athletes subject to anti-doping regulations must not use MT-1 in any form, including in jurisdictions where Scenesse is legally prescribed for EPP, without a valid Therapeutic Use Exemption (TUE). This information is for research reference only and does not constitute medical advice or a recommendation for human use outside of physician-supervised, approved indications.

Research summary

MT-1 (afamelanotide) has the most robust human evidence base of any peptide in the cosmetic tanning category, owing primarily to the clinical development programme that led to its regulatory approval for EPP. Two pivotal Phase III randomised, double-blind, placebo-controlled trials (the EU CUV029 trial, n=74; the US CUV039 trial, n=94) demonstrated statistically significant increases in pain-free sun exposure hours for EPP patients receiving 16 mg subcutaneous implants every 60 days. The primary endpoint in the US trial was met (median 69.4 hours afamelanotide vs. 40.8 hours placebo; p=0.04), as was the EU trial endpoint (median 6.0 vs. 0.8 hours; p=0.005). The long-term observational study by Biolcati et al. (British Journal of Dermatology, 2015) followed 115 patients across up to 8 years and 1,023 implants, documenting only minor adverse events predominantly consisting of nausea, with quality of life scores improving from 31% to 74% of maximum. Phase II data support preliminary efficacy in polymorphous light eruption and solar urticaria. Research in actinic keratosis prevention among organ-transplant recipients, vitiligo, and acne vulgaris was initiated but results were not published, and these indications have not advanced to Phase III. The mechanism — selective MC1R agonism driving eumelanin synthesis via cAMP-MITF-tyrosinase — is well characterised and pharmacologically sound. The short plasma half-life (~30 minutes) is established; the implant delivery system was specifically engineered to overcome this limitation by providing a rapid burst release over the first five days. The honest evidence grade for cosmetic tanning in healthy individuals is anecdotal. Clinical trials were conducted in EPP patients with severely impaired photoprotection — a population where even modest tanning provides clinically meaningful benefit. Whether the same dose and regimen produces acceptable safety and meaningful cosmetic tanning in eumelanin-replete, healthy adults with normal UV tolerance has not been studied in controlled trials. The WADA prohibition reflects the substance's classification as a peptide hormone with performance or appearance-modifying potential, not a finding of performance enhancement per se.

FAQ

What is the difference between MT-1 and MT-2?
Both are synthetic alpha-MSH analogues that stimulate melanin production, but they differ in receptor selectivity. MT-1 (afamelanotide) is highly selective for MC1R, the receptor on melanocytes responsible for skin pigmentation. MT-2 also activates MC3R and MC4R, which drive libido effects, spontaneous erections, appetite suppression, and significantly more nausea. MT-1's cleaner receptor profile means it does not produce the sexual side effects associated with MT-2. MT-1 has FDA/EMA approval for a medical indication (EPP); MT-2 does not.
Is MT-1 (afamelanotide) FDA-approved?
Yes — but only in a specific formulation and for a specific medical condition. Afamelanotide (Scenesse) received FDA approval in October 2019 for the prevention of phototoxic pain in adults with erythropoietic protoporphyria (EPP). The approved product is a 16 mg controlled-release subcutaneous implant administered by a clinician every 60 days. Injectable research-grade MT-1 is not FDA-approved for any use.
Does MT-1 cause melanoma?
Current evidence does not show that afamelanotide causes melanoma. Phase III trials, a long-term observational study covering 115 patients and over 1,000 implants across up to 8 years, and post-approval pharmacovigilance have not attributed any melanoma case to afamelanotide. Eumelanin — the pigment MT-1 promotes — is photoprotective and antioxidant in character. That said, the EMA required an ongoing post-approval safety study monitoring for nevi changes and melanoma, and individuals with numerous dysplastic nevi or a personal/family history of melanoma should consult a dermatologist before any use.
What are the most common side effects?
In Phase III clinical trials, the most commonly reported side effects with the 16 mg implant were nausea, headache, and implant-site hyperpigmentation, typically appearing shortly after implant insertion and resolving within 72 hours. Fatigue and dizziness were also reported. No drug-related serious adverse events were identified in the pivotal trials. The sexual arousal, appetite suppression, and prominent nausea associated with Melanotan II are not characteristic of MT-1 at therapeutic doses due to its MC1R selectivity.
Is MT-1 banned in sport?
Yes. Afamelanotide and related melanocortin peptides are prohibited under the WADA Prohibited List (Section S2, Peptide Hormones and Related Substances), at all times — in and out of competition. Athletes subject to anti-doping regulations require a valid Therapeutic Use Exemption (TUE) even if using the legally prescribed Scenesse implant for EPP.
How does the Scenesse implant work differently from an injection?
The Scenesse implant is an engineered controlled-release rod (~1.7 cm long) inserted subcutaneously that releases approximately 90% of its 16 mg dose within the first five days, producing a brief pharmacological burst rather than sustained blood levels. The plasma half-life of afamelanotide is approximately 30 minutes, so drug is largely undetectable within 10 days of implant. An injectable research peptide, by contrast, would follow that ~30-minute half-life directly, producing a shorter-lived pulse per dose. Injection frequency in community protocols is therefore higher than the once-per-60-days implant schedule.
Is research-grade injectable MT-1 the same as Scenesse?
No. Scenesse is a pharmaceutical-grade implant manufactured to strict GMP standards, with confirmed purity, controlled release kinetics, and clinical safety data for the approved route of administration. Research-grade injectable MT-1 is lyophilised powder produced without pharmaceutical quality oversight. It is sold for laboratory research use only. Purity, sterility, and actual peptide content are not guaranteed, and it has no regulatory approval for human use in any form or dose.

References

  1. Afamelanotide for Erythropoietic Protoporphyria (Langendonk et al., NEJM 2015) (study)
  2. Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria (Biolcati et al., BJD 2015) (study)
  3. Afamelanotide: A Review in Erythropoietic Protoporphyria (Kim & Garnock-Jones, Am J Clin Dermatol 2016) (review)
  4. A review and update on melanocyte stimulating hormone therapy: afamelanotide (Fabrikant et al., J Drugs Dermatol 2013) (review)
  5. Afamelanotide, an agonistic analog of α-MSH, in dermal phototoxicity of erythropoietic protoporphyria (Harms et al., PubMed 2011) (study)
  6. Afamelanotide — Wikipedia (pharmacology, approvals, pharmacokinetics) (review)
  7. Afamelanotide (Scenesse) — DermNet NZ clinical summary (review)

All content is for research and educational use only and is not medical advice. Products are sold for laboratory research only and are not for human consumption.