Researchers created a new skin‑darkening peptide made only of regular amino acids that strongly activates the MC1R receptor, which controls melanin production. In animal tests it darkened skin quickly and the effect wore off fast, suggesting it could give a short‑term tan without sun exposure. Because it avoids exotic building blocks, it may be safer than older versions, but it’s still early‑stage research.

Melanoma is a lethal form of skin cancer. Skin pigmentation, which is regulated by the melanocortin 1 receptor (MC1R), is an effective protection against melanoma. However, the endogenous MC1R agonists lack selectivity for the MC1R and thus can have side effects. The use of noncanonical amino acids in previous MC1R ligand development raises safety concerns. Here we report the development of the first potent and selective hMC1R agonist with only canonical amino acids. Using γ-MSH as a template, we developed a peptide, [Leu³, Leu⁷, Phe⁸]-γ-MSH-NH₂ (compound 5), which is 16-fold selective for the hMC1R (EC₅₀ = 4.5 nM) versus other melanocortin receptors. Conformational studies revealed a constrained conformation for this linear peptide. Molecular docking demonstrated a hydrophobic binding pocket for the melanocortin 1 receptor. In vivo pigmentation study shows high potency and short duration. [Leu³, Leu⁷, Phe⁸]-γ-MSH-NH₂ is ideal for inducing short-term skin pigmentation without sun for melanoma prevention.