Melanotan I 10mg

  • Brand:Full Catalog
  • Product Code: MT01
  • Availability: In Stock

  • $24.00

Afamelanotide (MT-1)




Afamelanotide, sometimes referred to as melanotan-1, also called NDP-MSH, is a synthetic alpha-melanocyte stimulating hormone (a-MSH) peptide analog first developed at the University of Arizona and later by Clinuvel, Inc. Afamelanotide (MT-1) acts on the melanocortin system and induces melanogenesis (skin pigmentation changes) in human and animal trials[1]; it is currently under review in the United States for treatment of UV photosensitivity in patients diagnosed with erythropoetic protoporphyria (EPP)[2].  Italian and Swiss regulatory agencies have given approval for limited use of afamelanotide for that indication. Other prospective drug uses of afamelanotide (MT-1) include repigmentation in vitiligo and prevention or reduction of UV damage (photoprotection) in sensitive individuals without EPP but with other specified indications, during sun exposure[3].  Clinuvel Pharmaceuticals first designated afamelanotide as CUV1467, but has received approval to use the name Scenesse in some European markets. As with other melanotropin peptides, melanotan-1 has received some notoriety for illicit use as a “sunless tanning” agent or as an aid to UV-induced tanning[4].


Use in EPP


Latest evidence (2015) suggests that afamelanotide is highly effective for treatment of erythropoetic protoporphyria, with approximately two-thirds of patients known to experts in the United States receiving afamelanotide as treatment; of those receiving treatment, the vast majority confirmed that their symptomatic relief met expectations, and with nausea being the primary adverse event reported among other minor adverse events [5].


Effects on Tanning and UV-B Exposure Outcome


In a three-part series of small open-label trials, conducted by Dorr et al at the University of Arizona in 2004, a significant effect size was demonstrated in several key areas related to tanning and UV-B exposure outcomes:


Tanning [was achieved in the majority of subjects] receiving MT-1[sic], and these subjects also had 47% fewer sunburn cells at the irradiated neck site. More skin sites darkened with the higher dose of MT-1 in the second study. In the third study, there was significantly enhanced tanning of the back in the MT-1 group, and this was maintained at least 3 weeks longer than the tanning in the sunlight-only controls, who required 50% more sun-exposure time for equivalent tanning[6].


In summary, afamelanotide was shown to reduce sunburn cells during UV exposure, result in darker tanning, and result in longer-lasting tanning with less sun exposure[6]. The 2004 trials confirmed earlier published results going back to 1991 or earlier, many of which had larger sample sizes[7].



Mini-review - Functional Relationships: Novel or Future Possibilities for Afamelanotide Development or Translational Research


In addition to treatment of porphyrias or other UV-sensitive conditions, repigmentation in vitiligo, and perhaps safer sunless tanning, afamelanotide has shown other intriguing effects that do not currently merit development by pharmaceutical firms, but which demonstrate the complexity and importance of the melanocortin system.


The biggest drug-development challenges, as with many peptide molecules, are 1) delivering the compound in a way that allows for a therapeutic effect in the target population and 2) exploiting the effect in the target population. These represent real challenges that may prevent afamelanotide and compounds like it from being developed in their own right for some time, but emerging data continue to suggest the promise of the melanocortin system as a therapeutic target or an area for further inquiry.


Challenges with delivery stem from the fact that complex peptide molecules do not easily pass through either the digestive tract or the epidermis due to fragility or other molecular characteristics. Delivery by subcutaneous, intravenous, or intramuscular means has been the primary means of preliminary investigation in published studies and trials[6,8]; however, historically, this is a route which is unattractive to drug developers since it introduces the challenge and cost of clinical administration, rather than self-administration. 


In treatment of EPP, a resorbable implant containing 16mg afamelanotide has shown promise in effectively treating the painful phototoxicity without requiring frequent followup clinical administrations due to the short half-life of afamelanotide, instead being replaced every 60 days[9]. Notably, the development of human antibodies to a-MSH/NDP-MSH in research to date, even with long-term (6 months or greater, up to 6 years) administration of afamelanotide, under proper observational settings, is low or nonexistent[10,11]. In other trials (Biolcati et al) a 20mg afamelantide resorbable implant has been used on a more frequent schedule with favorable results.



Endogenous alpha-MSH (a-MSH) plays a complex role in mammalian physiology; as a partial analog of alpha-MSH, afamelanotide or NDP-MSH has also demonstrated a diverse array of effects[9]. These diverse effects hold promise for future development or translational research.


Potential for Cardiac Research


In preliminary animal model studies investigating the effects of afamelanotide on the heart, a specific cardioprotective effect was observed in at least two different studies[12,13]. In looking to replicate and further earlier studies demonstrating that afamelanotide protected the animal heart against reperfusion injury or during transplantation,  Catania et al confirmed that phenotypic changes in the heart resemble the effects achieved through ischemic preconditioning[12]. Ischemic preconditioning is one of the most effective methods to protect a heart against reperfusion injury, leading to smaller myocardial infarction compared to control in every species studied[14]. Catalania et al speculate that the MC1R-mediated effect or a general anti-inflammatory effect may be responsible for the observed benefit[12], while Ottani and colleagues, using a potassium-chloride induced cardiac arrest model with CPR and epinephrine applied concurrent to afamelanotide immediately afterward, had more specific answers to the involved pathways:


In [group 1] CA/CPR rats i.v. treated with epinephrine (0.1 mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), ... left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10... On the other hand, [in group 2, with addition of afamelanotide] i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340 μg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels... These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway.[12]


Adding to the translational mystique of afamelanotide, survival rate of rats was boosted by a dramatic 81% when afamelanotide was coadministered after the cardiac event, as compared to the epinephrine- and- CPR-only group without afamelanotide[12].


Potential for Anti-Proliferative or Anti-Melanoma Research


Afamelanotide has been observed to have both a general anti-inflammatory effect as well as an antioxidant effect mediated by transcription factor Nrf2[15].


At various stages of research[16] it has also been touted as having a preventive (when administered prior to experimental insult, such as prior to UV damage[16]), protective (when co-administered with experimental insult), or therapeutic (when administered after experimental insult, or in clinical trials where a known condition exists) effect in various contexts.


The effects of afemelanotide on mole size, risk, and magnitude of damage after UV exposure has been discussed extensively[1,4,6], but the acknowledged[17,18] potential of afamelanotide to enable more precise study[17] or even contribute to better treatments of melanoma[18] has not been discussed extensively, by comparison, to date.


Highly preliminary results showed varied results in the following markers among seventeen different in vitro strains of human melanoma cell (HMC) cultures: tyrosinase activity upregulation, cell size changes, and activity of other enzymes when exposed at various times during incubation; however, of note, afamelanotide demonstrated an apparent anti-proliferative effect across multiple cell lines regardless of type, and these effects persisted even after it was removed from the cultures[20].


Promising areas for future inquiry include radiolabeled targeting of MSH peptides (such as afamelanotide, or modified configurations thereof) for MC1R-overexpressing melanoma lines[21], as well as further in vitro and, perhaps, eventual animal (in vivo) studies of the likely cytostatic[20] mechanisms through which afamelanotide has been shown to have a remarkable effect on some strains of HMC lines.





[1]Ann N Y Acad Sci. 1999 Oct 20;885:117-33.The melanocortin-1 receptor and human pigmentation.Abdel-Malek Z1, Suzuki I, Tada A, Im S, Akcali C.

[2]A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP). Identifier:NCT01605136a

[3]Lim HW, et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. JAMA Dermatol. 2015 Jan;151(1):42-50.

[4]MHRA National Archives [UK]. Subject: Melanotan. "Press release: 'Tan jab' is an unlicensed medicine and may not be safe - warns medicines regulator." 17 November 2008.

[5]Biolcati G, et al.  Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria. Br J Dermatol. 2015 Jun;172(6):1601-12.

[6]Dorr et al. Effects of a Sueprpotent Melanotropic Peptide in Combination with Solar UV Radiation on Tanning of the Skin in Human Volunteers. Arch Dermatol. 2004;140(7):827-835.

[7] Levine N, Sheftel SN, Eytan T; et al. (Nov 1991). "Induction of skin tanning by subcutaneous administration of a potent synthetic melanotropin". Journal of the American Medical Association, (JAMA) 266 (19): 2730–6.

[8]Luger TA, Bohm M. An α-MSH Analog in Erythropoietic Protoporphyria. Journal of Investigative Dermatology (2015) 135, 929–931.

[9]Langendonk, et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med 2015; 373:48-59

[10]Lengweiler S, et al. Evaluation of the Immunogenicity of the Synthetic α-Melanocyte-Stimulating Hormone (α-MSH) Analogue Afamelanotide ([Nle4-D-Phe7]-α-MSH, Scenesse®) in Erythropoietic Protoporphyria Patients by ELISA Detecting Both Anti-Afamelanotide and Anti-α-MSH Antibodies. Skin Pharmacol Physiol 2015;28:103-113.

[11]Spichty R, Balimann M, Barman J, Minder EI. A bioassay for the detection of neutralizing antibodies against the α-melanocyte stimulating hormone analog afamelanotide in patients with erythropoietic protoporphyria. J Pharm Biomed Anal. 2013 Mar 5;75:192-8.

[12]Catania A et al. The peptide NDP-MSH induces phenotype changes in the heart that resemble ischemic preconditioning. Peptides. 2010 Jan;31(1):116-22.

[13]Ottani A, et al. Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest. Eur J Pharmacol. 2014 Dec 15;745:108-16.

[14]Efstathios K , et al.  Ischemic preconditioning: Protection against myocardial necrosis and apoptosis. Vasc Health Risk Manag. 2007 Oct; 3(5): 629–637.

[15]Biolcati G. Efficacy of the melanocortin analogue Nle4-D-Phe7-α-melanocyte-stimulating hormone in the treatment of patients with Hailey–Hailey disease. Clin Exp Dermatol. 2014 Mar; 39(2): 168–175.

[16]Hadley ME, Dorr TR. Review. Melanocortin peptide therapeutics: Historical milestones, clinical studies and commercialization. Peptides: Volume 27, Issue 4, April 2006, Pages 921–930.

[17] Gehlsen KR, Hadley ME, Levine N, Ray CG, Hendrix MJC. (Nov 1992). "Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion.". Pigment Cell Res 5 (5): 219–23. doi:10.1111/j.1600-0749.1992.tb00540.x. PMID 1337602.

[18]Jiang J, Sharma SD, Nakamura S, Lai JY, Fink JL, Hruby VJ; et al. (Dec 1995). "The Melanotropic Peptide, [Nle4, d-Phe7]α-MSH, Stimulates Human Melanoma Tyrosinase Activity and Inhibits Cell Proliferation.". Pigment Cell Res 8 (6): 314–323. doi:10.1111/j.1600-0749.1995.tb00680.x. PMID 8789740.

[20]Hadley et al. The Melanotropic Peptide, [Nle4, d-Phe7]α-MSH, Stimulates Human Melanoma Tyrosinase Activity and Inhibits Cell Proliferation. Pigment Cell Research. Volume 8, Issue 6, pages 314–323, December 1995.

[21]Eberle AN, Bapst JP, Calame M, Tanner H, Froidevaux S. MSH radiopeptides for targeting melanoma metastases. Adv Exp Med Biol. 2010;681:133-42.



Write a review