Afamelanotide

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Chemical compound

title: "Afamelanotide" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["melanocortin-receptor-agonists", "orphan-drugs", "peptides"] description: "Chemical compound" topic_path: "general/melanocortin-receptor-agonists" source: "https://en.wikipedia.org/wiki/Afamelanotide" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

::data[format=table title="Infobox drug"]

FieldValue
Verifiedfieldschanged
Watchedfieldschanged
verifiedrevid477364562
imageMelanotan.png
image_classskin-invert-image
pronounce
tradenameScenesse
Drugs.com
DailyMedIDAfamelanotide
pregnancy_AUB1
routes_of_administrationSubcutaneous
ATC_prefixD02
ATC_suffixBB02
legal_AUS4
legal_BR
legal_CA
legal_DE
legal_NZ
legal_UKPOM
legal_USRx-only
legal_US_comment
legal_EURx-only
legal_EU_comment
legal_UN
legal_status
elimination_half-life30 minutes
index2_labelas salt
CAS_number_Ref
CAS_number75921-69-6
PubChem16154396
IUPHAR_ligand1324
DrugBankDB04931
ChemSpiderID_Ref
ChemSpiderID17310725
UNII_Ref
UNIIQW68W3J66U
KEGG_Ref
KEGGD10511
KEGG2_Ref
KEGG2D11334
ChEBI136034
ChEMBL_Ref
ChEMBL441738
synonyms[Nle4,D-Phe7]α-MSH; NDP-α-MSH; NDP-MSH; Melanotan; Melanotan-1; Melanotan I; EPT1647; CUV1647;
IUPAC_nameN-acetyl-L-seryl-L-tyrosyl-L-seryl-L-norleucyl-L-α-glutamyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valinamide
C78
H111
N21
O19
SMILESCCCCC(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CN=CN1)C(=O)NC(CC2=CC=CC=C2)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC3=CNC4=CC=CC=C43)C(=O)NCC(=O)NC(CCCCN)C(=O)N5CCCC5C(=O)NC(C(C)C)C(=O)N)NC(=O)C(CO)NC(=O)C(CC6=CC=C(C=C6)O)NC(=O)C(CO)NC(=O)C
StdInChI_Ref
StdInChI1S/C78H111N21O19/c1-5-6-19-52(91-75(116)61(41-101)97-72(113)57(34-46-24-26-49(103)27-25-46)94-74(115)60(40-100)88-44(4)102)68(109)92-54(28-29-64(105)106)70(111)96-59(36-48-38-83-42-87-48)73(114)93-56(33-45-16-8-7-9-17-45)71(112)90-53(22-14-31-84-78(81)82)69(110)95-58(35-47-37-85-51-20-11-10-18-50(47)51)67(108)86-39-63(104)89-55(21-12-13-30-79)77(118)99-32-15-23-62(99)76(117)98-65(43(2)3)66(80)107/h7-11,16-18,20,24-27,37-38,42-43,52-62,65,85,100-101,103H,5-6,12-15,19,21-23,28-36,39-41,79H2,1-4H3,(H2,80,107)(H,83,87)(H,86,108)(H,88,102)(H,89,104)(H,90,112)(H,91,116)(H,92,109)(H,93,114)(H,94,115)(H,95,110)(H,96,111)(H,97,113)(H,98,117)(H,105,106)(H4,81,82,84)/t52-,53-,54-,55-,56+,57-,58-,59-,60-,61-,62-,65-/m0/s1
StdInChIKey_Ref
StdInChIKeyUAHFGYDRQSXQEB-LEBBXHLNSA-N
::

| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 477364562 | image = Melanotan.png | image_class = skin-invert-image | width = | alt = | caption =

| pronounce = | tradename = Scenesse | Drugs.com = | MedlinePlus = | DailyMedID = Afamelanotide | pregnancy_AU = B1 | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Subcutaneous | class = | ATC_prefix = D02 | ATC_suffix = BB02 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = | legal_BR = | legal_BR_comment = | legal_CA = | legal_CA_comment = | legal_DE = | legal_DE_comment = | legal_NZ = | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = | legal_EU = Rx-only | legal_EU_comment = | legal_UN = | legal_UN_comment = | legal_status =

| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = 30 minutes | duration_of_action = | excretion =

| index2_label = as salt | CAS_number_Ref = | CAS_number = 75921-69-6 | CAS_supplemental = | PubChem = 16154396 | IUPHAR_ligand = 1324 | DrugBank_Ref = | DrugBank = DB04931 | ChemSpiderID_Ref = | ChemSpiderID = 17310725 | UNII_Ref = | UNII = QW68W3J66U | KEGG_Ref = | KEGG = D10511 | KEGG2_Ref = | IUPHAR_ligand2 = | KEGG2 = D11334 | ChEBI = 136034 | ChEMBL_Ref = | ChEMBL = 441738 | NIAID_ChemDB = | PDB_ligand = | synonyms = [Nle4,D-Phe7]α-MSH; NDP-α-MSH; NDP-MSH; Melanotan; Melanotan-1; Melanotan I; EPT1647; CUV1647;

| IUPAC_name = N-acetyl-L-seryl-L-tyrosyl-L-seryl-L-norleucyl-L-α-glutamyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valinamide | C = 78 | H = 111 | N = 21 | O = 19 | SMILES = CCCCC(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CN=CN1)C(=O)NC(CC2=CC=CC=C2)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC3=CNC4=CC=CC=C43)C(=O)NCC(=O)NC(CCCCN)C(=O)N5CCCC5C(=O)NC(C(C)C)C(=O)N)NC(=O)C(CO)NC(=O)C(CC6=CC=C(C=C6)O)NC(=O)C(CO)NC(=O)C | StdInChI_Ref = | StdInChI = 1S/C78H111N21O19/c1-5-6-19-52(91-75(116)61(41-101)97-72(113)57(34-46-24-26-49(103)27-25-46)94-74(115)60(40-100)88-44(4)102)68(109)92-54(28-29-64(105)106)70(111)96-59(36-48-38-83-42-87-48)73(114)93-56(33-45-16-8-7-9-17-45)71(112)90-53(22-14-31-84-78(81)82)69(110)95-58(35-47-37-85-51-20-11-10-18-50(47)51)67(108)86-39-63(104)89-55(21-12-13-30-79)77(118)99-32-15-23-62(99)76(117)98-65(43(2)3)66(80)107/h7-11,16-18,20,24-27,37-38,42-43,52-62,65,85,100-101,103H,5-6,12-15,19,21-23,28-36,39-41,79H2,1-4H3,(H2,80,107)(H,83,87)(H,86,108)(H,88,102)(H,89,104)(H,90,112)(H,91,116)(H,92,109)(H,93,114)(H,94,115)(H,95,110)(H,96,111)(H,97,113)(H,98,117)(H,105,106)(H4,81,82,84)/t52-,53-,54-,55-,56+,57-,58-,59-,60-,61-,62-,65-/m0/s1 | StdInChI_comment = | StdInChIKey_Ref = | StdInChIKey = UAHFGYDRQSXQEB-LEBBXHLNSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation =

Afamelanotide, sold under the brand name Scenesse, is a medication used to prevent phototoxicity and to reduce pain from light exposure for people with erythropoietic protoporphyria. It is a melanocortin 1 receptor (MC1 receptor) agonist and a synthetic peptide and analogue of α-melanocyte stimulating hormone. It is administered as subcutaneous implant.

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Medical uses

In the European Union, afamelanotide is indicated for the prevention of phototoxicity in adults with erythropoietic protoporphyria.

In the United States, afamelanotide is indicated for increasing pain-free light exposure in adults with a history of reactions to light (phototoxicity) from erythropoietic protoporphyria.

Adverse effects

Very common adverse effects include nausea and headache (may affect more than 10% of people). Common adverse effects include injection site reactions, back pain, upper respiratory tract infections, melanocyte naevus, decreased appetite, migraine, dizziness, weakness, fatigue, lethargy, sleepiness, hot flashes, abdominal pain, diarrhea, vomiting, flushing, development of warts, spots, and freckles, and itchy skin (between 1% and 10% of people). Uncommon and rare adverse effects include cystitis, folliculitis, gastrointestinal infections, hypersensitivity reactions, changes in appetite, depression, insomnia, balance disorders, lethargy, restless leg syndrome, syncope, photophobia, presbyopia, tinnitus, confusion, palpitations, hypertension, hypercholesterolaemia, and weight gain.

Pharmacology

Afamelanotide is a synthetic tridecapeptide and a structural analogue of α-melanocyte stimulating hormone (α-MSH). It is a melanocortin receptor agonist and binds predominantly to the MC1 receptor. Its binding lasts longer than that of α-MSH. This results in part from afamelanotide's resistance to immediate degradation by serum or proteolytic enzymes. It is thought to cause skin darkening by binding to the MC1 receptor which in turn drives melanogenesis.

It has a short half-life of approximately 30 minutes. After administration with implantation into the skin, the majority of the drug is released within two days, with 90% released by the fifth day. By the tenth day, no drug is detectable in plasma.

Drug distribution, metabolism and excretion were not understood as of 2017.

Chemistry

Afamelanotide has the amino acid sequence; Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2.

It is also known as [Nle4,D-Phe7]-α-MSH, which is abbreviated to NDP-MSH or NDP-α-MSH.

Afamelanotide is the international nonproprietary name.

History

α-MSH was first isolated in the 1950s and its primary structure determined. By the 1960s, its role in promoting melanin diffusion was understood.

In the 1980s, the University of Arizona synthesised more potent analogs of a-MSH, including afamelanotide. Afamelanotide was initially named melano-tan (or melanotan-I) due to its ability to tan skin with minimal sun exposure. Later, melanotan-II was synthesised.

Following initial development at the University of Arizona as a sunless tanning agent, the Australian company Clinuvel conducted further clinical trials in that and other indications, and brought the drug to market in the European Union, the United States, and Australia.

To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies, a technology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan, which changed its name to Clinuvel in 2006.

Early clinical trials showed that the peptide had to be injected about ten times a day due to its short half-life, so the company collaborated with Southern Research in the US to develop a depot formulation that would be injected under the skin, and release the peptide slowly. This was done by 2004.

Multiple studies on the clinical effects of afamelanotide were conducted. According to ClinicalTrials.gov, Clinuvel sponsored several trials between 2007 and 2011 to explore its effects on erythropoietic protoporphyria, vitiligo, polymorphous light eruption, solar urticaria and acne vulgaris. Additionally, one trial aimed to assess its role in preventing actinic keratosis in organ transplant recipients. Further trials were pursued for the first two conditions, while results for the latter three were not published. Following the initial trials, research efforts centered on erythropoietic protoporphyria, and due to the epidemiology of the condition. Clinuvel secured orphan drug for afamelanotide in both the US and the EU by 2010.

The first approval of afamelanotide came in May 2010 from the Italian Medicines Agency (AIFA, or Agenzia Italiana del Farmaco), followed by the European Medicines Agency (EMA) in January 2015. Both approvals were for the treatment of erythropoietic protoporphyria.

The US Food and Drug Administration (FDA) granted approval in October 2019 for the use of afamelanotide as a medication to alleviate pain caused by sun exposure in individuals with erythropoietic protoporphyria. This decision was largely based on three trials involving 244 adults aged 18–74 across 22 sites in the US and Europe, which had a focus on pain-free hours in sunlight, outdoor hours under varying light conditions, and side effects.

Between 2022 and 2023, trials were outlined to study the effects of afamelanotide on xeroderma pigmentosum and variegate porphyria, along with two additional trials exploring its impact on vitiligo. According to the register, as of April 2025, most of these trials are currently in the recruitment phase.

Society and culture

Usage in general public

A number of products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" which discuss afamelanotide in their marketing.

Without a prescription, these drugs are not legally sold in many jurisdictions and are potentially dangerous.

Starting in 2007, health agencies in various countries began issuing warnings against their use.

References

References

  1. (15 May 2023). "Scenesse- afamelanotide implant". U.S. National Library of Medicine.
  2. (8 October 2019). "Drug Trials Snapshots: Scenesse".
  3. (31 December 2019). "New Drug Therapy Approvals 2019".
  4. (27 January 2016). "Scenesse: Summary of Product Characteristics". [[European Medicines Agency]] (EMA).
  5. (17 September 2018). "Scenesse EPAR".
  6. (2009). "International Nonproprietary Names for Pharmaceutical Substances (INN)". [[World Health Organization]] (WHO).
  7. (May 1993). "The role of melanin-concentrating hormone in color change". Annals of the New York Academy of Sciences.
  8. (October 1980). "4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity". Proceedings of the National Academy of Sciences of the United States of America.
  9. (1992). "Preformulation studies of melanotan-II". [[University of Arizona]].
  10. (December 1989). "Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics". Journal of Medicinal Chemistry.
  11. (1 November 2004). "EpiTan focuses on Melanotan, a potential blockbuster". The Pharma Letter.
  12. (April 2006). "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization". Peptides.
  13. (27 February 2006). "Epitan changes name to Clinuvel, announces new clinical program". LabOnline.
  14. (October 2017). "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review". International Journal of Dermatology.
  15. (September 2010). "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?". The British Journal of Dermatology.
  16. Clinuvel Pharmaceuticals Limited. (2021-02-25). "A Phase III, Randomised, Double Blind, Placebo Controlled, Parallel Group Study, to Evaluate the Safety and Efficacy of Subcutaneous Implants of Afamelanotide (16 mg) in Patients Suffering From Polymorphic Light Eruption (PLE)". clinicaltrials.gov.
  17. Wright, Dr Dennis. (2009-09-13). "A Phase II, Open Label Pilot Study to Evaluate the Safety and Efficacy of A Bioresorbable Subcutaneous Implant of CUV1647 in Patients With Solar Urticaria (SU)". clinicaltrials.gov.
  18. Clinuvel Pharmaceuticals Limited. (2021-09-28). "A Phase II, Randomised, Open Label Pilot Study to Evaluate the Efficacy and Safety of Two Dosage Regimens of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Mild to Moderate Acne Vulgaris". clinicaltrials.gov.
  19. (2010-12-03). "A Multicentre, Randomised, Double-Blind, Placebo Controlled, Phase II Study to Evaluate the Safety and Efficacy of Subcutaneous Bioresorbable Implants of Afamelanotide (CUV1647) for the Prophylactic Treatment of Pre-Cancerous Skin Lesions of the Head, Forearms and Hands in Immune Compromised, Organ Transplant Patients.". clinicaltrials.gov.
  20. Clinuvel Pharmaceuticals Limited. (2019-10-08). "A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)". clinicaltrials.gov.
  21. Clinuvel Pharmaceuticals Limited. (2013-03-21). "Proof of Concept Study to Compare Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants and Narrow-Band Ultraviolet B (NB-UVB) Light Versus NB-UVB Light Alone in the Treatment of Nonsegmental Vitiligo". clinicaltrials.gov.
  22. Clinuvel Pharmaceuticals Limited. (2013-03-21). "A Phase II Randomised Pilot Study to Compare the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental Vitiligo". clinicaltrials.gov.
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  24. (2010). "Gazzetta Ufficiale: Sommario". [[Agenzia Nazionale Stampa Associata]].
  25. (8 October 2019). "FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder".
  26. (20 May 2009). "Believe It Or Not 'Tanorexia' A Very Real Problem". [[WCBS-TV]], [[CBS]].
  27. (14 June 2009). "Fools Gold". [[Cosmopolitan (magazine).
  28. (29 January 2009). "Suntan Drug Greenlighted for Trials".
  29. (31 October 2009). "Tanning drug a health risk". [[Herald Sun]].
  30. (September 2010). "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?". The British Journal of Dermatology.
  31. (January 2009). "Change in moles linked to use of unlicensed "sun tan jab"". BMJ.
  32. (18 February 2009). "Risky tan jab warnings 'ignored'". [[BBC News Online]].
  33. (2008). "Warning against the product Melanotan". [[Danish Medicines Agency]].
  34. (2008). ""Tan jab" is an unlicensed medicine and may not be safe". [[Medicines and Healthcare products Regulatory Agency]] (MHRA).
  35. (29 January 2009). "US Lab Research Inc Warning letter". U.S. [[Food and Drug Administration]] (FDA).
  36. (2009). "Melanotan Powder for Injection". [[Irish Medicines Board]].
  37. (13 December 2007). "Legemiddelverket advarer mot bruk av Melanotan". Norwegian Medicines Agency.
  38. (23 January 2009). "Melanotan – farlig og ulovlig brunfarge". [[Norwegian Medicines Agency]].

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melanocortin-receptor-agonistsorphan-drugspeptides