Melanotan-1 (Melanota)

Melanotan-1 (also referenced in research literature as NDP-MSH and afamelanotide) is a synthetic linear 13-amino-acid research peptide engineered as a structural analog of alpha-melanocyte-stimulating hormone (alpha-MSH). It is supplied as an investigational laboratory peptide for use in melanocortin-1-receptor (MC1R) pharmacology research, melanocyte-signaling research, and structure-activity studies on linear alpha-MSH analogs.

Melanotan-1 is investigated in laboratory research studies as a probe compound for MC1R receptor pharmacology research, with retained activity at MC3R, MC4R, and MC5R in comparative receptor-binding research. The molecule's Nle4 and D-Phe7 substitutions confer enhanced enzymatic stability and prolonged receptor engagement relative to native alpha-MSH in cellular research models (Sawyer et al., 1980, PNAS).

Beyond receptor-binding research, Melanotan-1 has been investigated in cellular research models examining cAMP signaling research, MITF transcription factor research, and downstream melanocyte-signaling cascades following MC1R engagement. Structure-activity research has also characterized the molecule's receptor-binding geometry in comparative pharmacology studies across the melanocortin-receptor family (Frandberg et al., 1994, Biochemical and Biophysical Research Communications).

The peptide is supplied as a lyophilized powder to ensure optimal stability during storage and handling.

Melanotan-1 was developed as a linear synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous 13-amino-acid melanocortin peptide derived from proopiomelanocortin (POMC). Native alpha-MSH exhibits limited enzymatic stability in laboratory research environments, with a short plasma half-life that constrains its use as a research probe. This stability limitation motivated the engineering of structurally modified linear analogs.

The Melanotan-1 scaffold introduces two key amino-acid substitutions relative to native alpha-MSH. First, methionine at position 4 is replaced with norleucine (Nle4), which eliminates a methionine-oxidation site and improves stability in laboratory research solutions. Second, phenylalanine at position 7 is replaced with its D-enantiomer (D-Phe7), which confers resistance to enzymatic degradation and extends the molecule's pharmacokinetic profile in research models.

Together these substitutions produce a research compound that is reported in structure-activity research as substantially more potent than native alpha-MSH in cellular adenylyl cyclase research assays, while retaining the linear 13-amino-acid backbone characteristic of the parent peptide. This profile has made Melanotan-1 a widely used reference compound in laboratory research studies of MC1R receptor pharmacology, melanocortin-receptor structure-activity research, and comparative GPCR pharmacology across the melanocortin-receptor family.

1. MC1R Receptor Engagement

Melanotan-1 engages melanocortin-1-receptor (MC1R), a class A G-protein-coupled receptor broadly investigated in melanocyte-signaling research and laboratory research models of melanocortin-receptor pharmacology. Laboratory research studies report nanomolar binding affinity at MC1R in cellular research models, with retained binding affinity at MC3R, MC4R, and MC5R in comparative receptor-binding research (Frandberg et al., 1994).

2. Modulation of Cyclic AMP Signaling

Upon MC1R engagement, Melanotan-1 modulates Gαs-coupled adenylyl cyclase activity, producing intracellular cyclic AMP accumulation. Structure-activity research has reported this analog as substantially more potent than native alpha-MSH in cellular adenylyl cyclase research assays, making it a frequently used reference compound in melanocortin-receptor signaling research (Sawyer et al., 1980).

3. Nle4 and D-Phe7 Substitution Pharmacology

The Nle4 substitution eliminates a methionine-oxidation site, while the D-Phe7 substitution confers resistance to enzymatic degradation in cellular research models. Together these modifications extend the molecule's biological half-life and produce a prolonged receptor-engagement profile relative to native alpha-MSH in laboratory research studies.

4. Downstream MITF and Melanogenic Gene Research

MC1R-coupled cAMP accumulation modulates protein kinase A (PKA) activity, CREB phosphorylation research, and downstream microphthalmia-associated transcription factor (MITF) signaling research in cellular research models. Melanotan-1 is investigated as a probe compound for examining these downstream melanocyte-signaling cascades in laboratory research environments.

Research Applications

Conclusion

Melanotan-1 represents a linear 13-amino-acid synthetic analog of alpha-MSH that has become a widely used reference research compound in MC1R receptor pharmacology research. Its Nle4 and D-Phe7 substitutions, characterized cAMP signaling profile, and structure-activity data across the melanocortin-receptor family make it a valuable investigational laboratory peptide for studies of melanocortin-receptor pharmacology research and class A GPCR signaling research models.

Research Use Disclaimer

This product is intended for research and laboratory use only. It is designed exclusively for in vitro research purposes. All information provided is for educational and research reference only. This product is not intended for human or animal use. It is not a drug, food, or cosmetic and must not be marketed, labeled, or used as such. Use and handling are restricted to trained and qualified professionals.