Melanotan 2

Melanotan 2 (also referenced in research literature as MT-II) is a synthetic cyclic heptapeptide research compound classified as a non-selective melanocortin-receptor agonist. It is supplied as an investigational laboratory peptide for use in melanocortin-receptor pharmacology research, melanocyte-signaling research, and GPCR structure-activity studies across the MC1R, MC3R, MC4R, and MC5R receptor subtypes.

Melanotan 2 is investigated in laboratory research studies as a non-selective probe compound for melanocortin-receptor pharmacology research. The molecule is engineered with a lactam bridge that constrains its cyclic conformation, supporting receptor-binding research at all four melanocortin-receptor subtypes engaged by alpha-MSH (Bednarek et al., 2007, Journal of Medicinal Chemistry).

Beyond melanocortin-receptor engagement research, Melanotan 2 is investigated in cellular research models examining cAMP signaling research, GPCR pharmacology, and downstream second-messenger cascades following melanocortin-receptor activation. The lactam-bridged scaffold has also been characterized in structural pharmacology research for its constrained receptor-binding geometry (Hruby et al., 2018, PMC).

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

Melanotan 2 was developed as a cyclic, lactam-bridged synthetic analog of alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous melanocortin peptide derived from proopiomelanocortin (POMC). Native alpha-MSH is a linear 13-amino-acid peptide with limited enzymatic stability in laboratory research environments, which has motivated the engineering of constrained cyclic analogs for melanocortin-receptor pharmacology research.

The Melanotan 2 scaffold incorporates two key engineering features. First, methionine at position 4 of the parent alpha-MSH sequence is replaced with norleucine (Nle4), which eliminates a methionine-oxidation site and improves stability in laboratory research solutions. Second, a lactam bridge between Asp and Lys residues enforces a constrained beta-turn conformation that pre-organizes the molecule for receptor binding across the melanocortin-receptor family.

This combination of substitutions and cyclic constraint makes Melanotan 2 a non-selective agonist of MC1R, MC3R, MC4R, and MC5R, supporting its use as a probe compound in laboratory research studies of melanocortin-receptor pharmacology, comparative GPCR research, and structure-activity research on cyclic melanocortin analogs.

1. Non-Selective Melanocortin-Receptor Engagement

Melanotan 2 engages all four alpha-MSH-responsive melanocortin-receptor subtypes (MC1R, MC3R, MC4R, MC5R) in cellular research models. Each of these receptors is a class A G-protein-coupled receptor that couples primarily to Gαs, supporting laboratory research studies of non-selective melanocortin-receptor pharmacology and comparative receptor engagement research.

2. Modulation of Cyclic AMP Signaling

Upon engagement with melanocortin receptors, Melanotan 2 modulates adenylyl cyclase activity, producing intracellular cyclic AMP accumulation. This second-messenger response is the primary investigated output in melanocortin-receptor signaling research and supports downstream modulation of PKA and CREB-dependent transcription research in cellular research models.

3. Lactam-Bridge Conformational Constraint

Structural pharmacology research has characterized the Asp-Lys lactam bridge as enforcing a beta-turn conformation that pre-organizes Melanotan 2 for melanocortin-receptor engagement. This conformational constraint is a frequent subject of structure-activity research and is investigated as the basis for the molecule's broad activity across the melanocortin-receptor family (Bednarek et al., 2007).

4. MC1R-Mediated Melanocyte Signaling Research

Melanotan 2 is investigated in laboratory research studies of MC1R-mediated melanocyte signaling, where MC1R engagement modulates cAMP accumulation, MITF transcription factor signaling research, and downstream melanogenic gene-expression research in cellular research models.

Research Applications

Conclusion

Melanotan 2 represents a lactam-bridged, non-selective cyclic heptapeptide research compound that engages all four alpha-MSH-responsive melanocortin-receptor subtypes. Its constrained scaffold, broad receptor pharmacology profile, and characterized cAMP signaling output make it a valuable investigational laboratory peptide for studies of melanocortin-receptor pharmacology research, GPCR structure-activity 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.