A gel-forming α-MSH analog promotes lasting melanogenesis

Eur J Pharmacol. 2023 Nov 5:958:176008. doi: 10.1016/j.ejphar.2023.176008. Epub 2023 Sep 4.


The α-MSH peptide plays a significant role in the regulation of pigmentation via the melanocortin 1 receptor (MC1R). It increases the DNA repair capacity of melanocytes and reduces the incidence of skin cancers. As such, α-MSH analogs could have the utility for protecting against UV-induced skin DNA damage in susceptible patients. Recently, α-MSH analogs have been approved for the treatment of erythropoietic protoporphyria, hypoactive sexual desire, or pediatric obesity. However, the delivery of these drugs requires inconvenient implants or frequent injections. We recently found that select palmitoylated melanocortin analogs such as afamelanotide and adrenocorticotropin peptides self-assemble to form liquid gels in situ. To explore the utility of these novel analogs, we studied their pharmacological characteristics in vitro and in vivo. Acylated afamelanotide (DDE 313) and ACTH1-24 (DDE314) analogs form liquid gels at 6-20% and have a significantly increased viscosity at >2.5% compared to original analogs. Using the DDE313 analog as a prototype, we showed gel-formation reduces the passage of DDE313 through Centricon filters, and subcutaneous injection of analog gel in rats leads to the sustained presence of the peptide in circulation for >12 days. In addition, DDE313 darkened the skin of frogs for >4 weeks, whereas those injected with an equivalent dose of afamelanotide lost the tanning response within a few days. Because self-assembled gels allow sustained activation of melanocortin receptors, further studies of these analogs may allow the development of effective and convenient tanning therapies to prophylactically protect against UV-induced malignant transformation of skin cells in susceptible patients.

Keywords: MC1R; Melanogenesis; Melanoma; Photoprotection; Self-assemble; α-MSH.

MeSH terms

  • Animals
  • Gels / pharmacology
  • Melanocytes
  • Rats
  • Skin
  • Skin Neoplasms*
  • alpha-MSH* / pharmacology


  • alpha-MSH
  • Gels