Melanotan-2 (MT-II)
A synthetic cyclic lactam analogue of α-MSH, used as a reference compound in receptor structure-function (GPCR) studies.
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 receptors. This page summarises its molecular profile, its use in receptor studies, and the foundational published literature for laboratory reference only.
Molecular Profile
Use in Receptor Research
The following summarises how MT-II has been used in published in-vitro receptor research:
- Cross-subtype reference ligand: Published binding assays report MT-II affinity across several cloned melanocortin receptor subtypes (MC1R, MC3R, MC4R, MC5R), in contrast to subtype-selective ligands. MC2R is the ACTH-selective subtype and shows minimal MT-II binding in these assays.
- cAMP / Gs signalling: Melanocortin receptors are class A GPCRs coupled to Gs. In transfected cell lines, MT-II is used as a reference ligand in cAMP-accumulation assays across the subtypes.
- Structure-activity comparator:Because its cyclic scaffold is well characterised, MT-II is used as a benchmark when new linear and cyclic α-MSH analogues are synthesised and compared in receptor-binding and selectivity studies.
- 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 higher potency and stability relative to linear α-MSH in published in-vitro 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) and its molecular-dynamics-guided design.
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.
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization
Hadley ME, Dorr RT. Peptides. 2006; 27(4):921-930
Historical review placing MT-II and related analogues in the context of melanocortin receptor research 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 reference compound in melanocortin receptor structure-function studies, supplied as a lyophilised powder at ≥98% HPLC purity for in-vitro laboratory research only.
Which receptors has MT-II been studied with?
Published in-vitro binding assays report affinity across MC1R, MC3R, MC4R, and MC5R, with minimal binding at MC2R (the ACTH-selective receptor). This cross-subtype profile is why it is used as a reference ligand 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.