Melanotan II

Description

Overview

Melanotan II (MT-II) is a synthetic cyclic heptapeptide analog of endogenous α-melanocyte-stimulating hormone (α-MSH). Developed to address the rapid enzymatic breakdown of native linear melanocortin peptides, MT-II incorporates a lactam ring bridge alongside Nle⁴ and D-Phe⁷ amino acid modifications.

In research applications, Melanotan II functions as a potent agonist across melanocortin receptor subtypes (MC1R, MC3R, MC4R, MC5R). It is widely utilized in studies examining melanogenesis signaling, central appetite and metabolic regulation, neurobiological pathways, and cyclic peptide stability dynamics.

Key Technical Specifications

Sequence	Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
Molecular Formula	C₅₀H₆₉N₁₅O₉
Molecular Weight	~1024.18 g/mol
CAS Number	121062-08-6
Elimination Half-Life	~33 minutes (in vivo plasma residence)
Solubility	Bacteriostatic Water / Sterile Water
Primary Class	Non-Selective Melanocortin Receptor Agonist

Biochemical Architecture & Receptor Pharmacology

1. Structural Stabilization Chemistry

The covalent side-chain lactam bridge between Asp⁵ and Lys¹⁰ creates a rigid, cyclic β-turn structure. Combined with D-Phe⁷ substitution and terminal capping, this architecture provides significant resistance against cleavage by serum endopeptidases.

2. Melanocortin Subtype Activation Profile

• MC1R Signaling: Stimulates cAMP cascades in melanocytes to upregulate tyrosinase and drive eumelanin synthesis.
• MC3R / MC4R Engagement: Activates central hypothalamic receptors involved in satiety signaling, energy homeostasis, and autonomic pathways.
• MC5R Interactions: Engaged in exocrine gland signaling and peripheral lipid pathway investigations.

Academic Origin: Developed at the University of Arizona in the late 1980s, Melanotan II serves as a foundational reference compound in structure-activity relationship (SAR) literature for cyclic peptide drug design and central melanocortin receptor mapping.

For laboratory research, educational, and analytical reference only. Strictly not for human or veterinary use.