Afamelanotide

from Wikipedia, the free encyclopedia
Structural formula
Structure of Melanotan I
General
Non-proprietary name Afamelanotide
other names
  • Melanotan
  • Melanotan I
  • Melanotan-1
  • 4- L -Norleucine-7- D -Phenylalanine-α-Melanocyte-Stimulating Hormone (NDP-α-MSH)
Molecular formula C 78 H 111 N 21 O 19
External identifiers / databases
CAS number 75921-69-6
PubChem 16197727
ChemSpider 17310725
DrugBank DB04931
Wikidata Q410794
Drug information
ATC code

D02 BB02

properties
Molar mass 1646.85 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Afamelanotide ( Melanotan I , formerly CUV1647), also NDP-α-MSH, is a synthetic peptide hormone that mimics the effects of the natural hormone α-MSH . However, due to targeted changes in its chemical structure, it is much more effective than the natural variant. This is due to a longer half-life compared to α-MSH and a significantly stronger bond to the melanocortin receptor ( MC1R ). Afamelanotide stimulates melanin ( eumelanin ) production in melanocytes .

Use as a medicine

On December 22nd, 2014, the European Commission granted "Scenesse" a drug approval for the treatment of adult patients with erythropoietic protoporphyria (EPP) throughout the European Union . Before and during periods of high exposure to sunlight, e.g. B. from spring to autumn, the patient is injected every two months a rod-shaped implant under the skin.

The drug was developed by the Australian company Clinuvel Pharmaceuticals (formerly Epitan). The US Food and Drug Administration (FDA) has classified Melanotan I as an orphan drug for the treatment of erythropoietic protoporphyria . It was approved in the USA in October 2019.

Use

"Scenesse" extends the time that patients can spend in sunlight without pain. In a study with 93 EPP patients, patients treated with "Scenesse" spent an average of 116 hours ( arithmetic mean ) or 69 hours ( median ) in direct sunlight without pain during a six-month period, while patients treated with placebo only spent 61 hours (arithmetic mean ) or 41 hours (median).

Side effects

The most common side effects are nausea (19%), headache (20%) and reactions at the implant site (21%; predominantly discoloration, pain, bruises, erythema).

Risk management

"Scenesse" has been approved under so-called "exceptional circumstances". This means that due to the rarity of the disease, it was not possible to obtain complete information on the benefits and risks of "Scenesse" at the time of approval. To ensure its safe and effective use, a risk management plan has been developed to ensure that Scenesse is used as safely as possible. The European Medicines Agency will review every year any new information that may become available. A patient registry will provide long-term data on the drug's benefit and safety. Doctors are provided with a training film on correct use. The use of "Scenesse" is only permitted in specialized hospitals.

Chemical structure

Afamelanotide is of 13 amino acids existing peptide having the primary structure of Ac-Ser-Tyr-Ser-Nle-Glu-His- D -Phe-Arg-Trp-Gly-Lys-Pro-Val-NH 2 . In comparison to the α-MSH, two amino acids are exchanged: Met 4 → Nle 4 and L -Phe 7 → D -Phe 7 .

Individual evidence

  1. ↑ a b Data sheet (Nle 4 , D-Phe 7 ) -α-Melanocyte Stimulating Hormone trifluoroacetate salt from Sigma-Aldrich , accessed on June 16, 2011 ( PDF ).
  2. ↑ http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Summary_for_the_public/human/002548/WC500182310.pdf
  3. ↑ http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Product_Information/human/002548/WC500182307.pdf
  4. ↑ Phase III Trial of CUV1647 in Polymorphic Light Eruption (PLE) (English).
  5. ↑ Clinuvel Pharmaceuticals company announcement of July 29, 2008 ( Memento of December 5, 2008 in the Internet Archive ) (English; PDF; 53 kB).
  6. ↑ FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder. In: FDA. October 8, 2019, accessed March 16, 2020 .
  7. ↑ http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Summary_for_the_public/human/002548/WC500182310.pdf
  8. ↑ http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002548/WC500182309.pdf
  9. ↑ http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Product_Information/human/002548/WC500182307.pdf
  10. ↑ http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Summary_for_the_public/human/002548/WC500182310.pdf
  11. ↑ http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Risk-management-plan_summary/human/002548/WC500176263.pdf
  12. ↑ Hadley, ME & Dorr, RT (2006): Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. In: Peptides. Vol. 27, pp. 921-930. PMID 16412534

See also

Web links

Commons : 3D animated molecular structure and molecular information of Melanotan I and II  - album with pictures, videos and audio files