Melanotan II: Cyclic Alpha-MSH Analog Research Overview

Melanotan II was developed by Hadley, Hruby and colleagues in the late 1980s as a structural simplification of Melanotan I. By cyclizing a heptapeptide containing the alpha-MSH active core (His-Phe-Arg-Trp), the researchers produced a smaller, more conformationally constrained compound with retained receptor activity.^[1]

The compound's smaller size and more rigid structure result in altered pharmacokinetics relative to Melanotan I, including improved blood-brain barrier penetration in preclinical models. This led to a research line examining MT-II central nervous system effects, particularly in appetite and sexual response circuits.^[2]

Melanotan II is studied as a research reference compound in melanocortin receptor pharmacology. It has not been approved by the FDA for any human therapeutic or medical purpose.

Melanotan II structural features:

• Length: 7 amino acids (cyclic)

• Sequence: cyclic Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ — a lactam ring connecting Asp side chain to Lys epsilon-amine

• Active core: retains the His-Phe-Arg-Trp sequence from alpha-MSH (essential for melanocortin receptor binding)

• Cyclization: lactam bridge between Asp and Lys, imposing defined backbone geometry

• Molecular formula: C₅₀H₆₉N₁₅O₉

• Molecular weight: approximately 1,024 Da

The lactam cyclization forces the peptide to adopt a defined three-dimensional structure that mimics the bioactive conformation of native alpha-MSH. Compared to linear Melanotan I, the cyclic form sacrifices some receptor selectivity in exchange for conformational stability and improved pharmacokinetics — both common engineering trade-offs in peptide design.^[1][3]

Comparison to PT-141: PT-141 (Bremelanotide) shares the cyclic heptapeptide architecture but has a free C-terminal carboxylic acid instead of MT-II's amidated lysine. This single change shifts the receptor selectivity profile between the two compounds.

Melanotan II is a pan-agonist at melanocortin receptors.

MT-II shows agonist activity at MC1R, MC3R, MC4R, and MC5R. This pan-receptor profile makes it useful as a broad melanocortin pathway probe but less suited for studies requiring receptor subtype selectivity.^[3]

The smaller cyclic structure of MT-II is associated with better blood-brain barrier penetration than the linear Melanotan I in animal models. This makes MT-II useful for research questions involving central melanocortin pathways — particularly MC4R-mediated effects in hypothalamic appetite and sexual response circuits.^[4]

MT-II research spans multiple preclinical domains.

Cell-based studies of melanocyte pigmentation responses use MT-II as a reference agonist. The compound's MC1R activity produces robust tyrosinase activation and melanin synthesis in cultured melanocytes.^[5]

Hypothalamic MC4R signaling regulates food intake in animal models. MT-II is used as a tool for stimulating this pathway in rodent feeding behavior studies.^[4]

Central melanocortin signaling pathways involved in sexual response were initially identified using broad melanocortin agonists like MT-II. Subsequent work led to development of MC4R-selective agonists for this research line.^[6]

MT-II's cyclic structure provides excellent stability. Standard peptide handling applies.

Lyophilized material is stored at minus 20 degrees Celsius. The cyclic structure is robust to standard storage conditions.

Bacteriostatic water or sterile water are standard reconstitution solvents.

HPLC for purity, mass spectrometry for identity confirmation including verification of intact lactam cyclization, and endotoxin screening. Each batch of Instant Peptides Melanotan II ships with a full Certificate of Analysis.

Instant Peptides supplies Melanotan II as a synthetic lyophilized reference compound in 10mg vials. Material is supplied to qualified research professionals. Not for human or animal consumption.

View the product page for current pricing and the Certificate of Analysis for the active batch.