Melanotan-2 (MT-II)
A synthetic cyclic lactam analogue of α-MSH, studied as a non-selective melanocortin receptor agonist and reference tool compound in laboratory models.
Overview
Melanotan-2 (MT-II) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (α-MSH), one of the endogenous melanocortin peptides. It was designed at the University of Arizona using molecular-dynamics-guided structure-activity work to produce a conformationally constrained α-MSH fragment with markedly enhanced potency and proteolytic stability relative to the native hormone.
As a research reagent, MT-II is of interest because the melanocortin receptor family (MC1R-MC5R) is a long-standing target in G-protein- coupled receptor (GPCR) pharmacology. Its broad cross-reactivity across several receptor subtypes makes it a useful comparator in radioligand-binding assays, cAMP-accumulation assays, and structure-function studies of melanocortin signalling. This page summarises its molecular profile, receptor pharmacology, and the foundational published literature for laboratory reference only.
Molecular Profile
Mechanism of Action
The following describes receptor pharmacology characterised in published in-vitro research:
- Non-selective melanocortin receptor agonist: MT-II binds and activates multiple melanocortin receptor subtypes (MC1R, MC3R, MC4R, MC5R), in contrast to subtype-selective ligands. MC2R is activated essentially only by ACTH and shows minimal MT-II binding.
- cAMP / Gs signalling: Melanocortin receptors are class A GPCRs coupled to Gs; agonist binding stimulates adenylate cyclase and raises intracellular cAMP. MT-II is used as a reference agonist in cAMP-accumulation assays across the subtypes.
- Melanogenesis-pathway research (MC1R): At MC1R, melanocortin agonism is the canonical upstream trigger in cell-based melanogenesis models (cAMP to downstream pigment-synthesis signalling). MT-II serves as a superpotent positive control in such in-vitro cellular assays.
- Conformational constraint drives potency:The Asp-Lys lactam bridge and the D-Phe substitution rigidify the pharmacophore and confer resistance to proteolytic degradation, the structural basis for MT-II's superpotent and prolonged activity relative to linear α-MSH in published assays.
Key Published Research
Potent and prolonged-acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics
Al-Obeidi F, Castrucci AM, Hadley ME, Hruby VJ. Journal of Medicinal Chemistry. 1989; 32(12):2555-2561
The foundational design paper introducing the cyclic lactam α-MSH analogue (the MT-II pharmacophore), reporting superpotent activity in tyrosinase bioassays.
Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide
Dorr RT, et al. Life Sciences. 1996; 58(20):1777-1784
Early characterisation of the MT-II peptide and its melanotropic receptor activity.
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization
Hadley ME, Dorr RT. Peptides. 2006; 27(4):921-930
Review placing MT-II and related analogues in the context of melanocortin receptor pharmacology and proteolytic stability.
Storage and Handling
Lyophilised (unreconstituted):Store at -20°C; stable long-term when kept dry and sealed. Protect from light and moisture.
Reconstituted:Store at 2-8°C. Use within 30 days. Avoid repeated freeze-thaw cycles.
Recommended solvent: Bacteriostatic water or sterile water for laboratory use.
Frequently Asked Questions
What is MT-II?
MT-II (Melanotan-2) is a synthetic cyclic lactam heptapeptide analogue of α-MSH used as a non-selective melanocortin receptor agonist research reagent, supplied as a lyophilised powder at ≥98% HPLC purity for in-vitro laboratory research only.
Which receptors does MT-II act on?
In published binding and functional assays it shows agonist activity across MC1R, MC3R, MC4R, and MC5R, with minimal activity at MC2R (the ACTH-selective receptor). This broad cross-reactivity is why it is used as a reference melanocortin agonist rather than a subtype-selective tool.
How should MT-II be stored?
As a lyophilised powder at -20°C. Once reconstituted with bacteriostatic or sterile water, keep at 2-8°C and use within roughly 30 days, avoiding freeze-thaw cycles.
Disclaimer: This information is compiled from published peer-reviewed literature and is provided for educational and research reference purposes only. It does not constitute medical advice. Melanotan-2 sold by Enhanced Research Compounds is intended exclusively for in-vitro research and laboratory use. It is not a therapeutic good, is not listed on the ARTG, and is not approved for human or animal consumption.