MT-2 (Melanotan 2) is a cyclic synthetic heptapeptide analog of α-melanocyte-stimulating hormone (α-MSH), developed at the University of Arizona by the Hadley and Hruby laboratories in the 1980s. It is a non-selective agonist at melanocortin receptors MC1R, MC3R, MC4R, and MC5R (with weak activity at MC2R). The molecule was designed as a metabolically stable, conformationally constrained α-MSH analog for melanocortin pharmacology research. It is a research peptide and is not an approved medicine.

Is MT-2 the same as afamelanotide (Scenesse)?

No. MT-2 is the cyclic non-selective compound described on this page. Afamelanotide (also called Melanotan-1) is a separate, structurally distinct linear MC1R-selective analog ([Nle⁴,D-Phe⁷]-α-MSH) developed by Clinuvel Pharmaceuticals and approved as Scenesse for erythropoietic protoporphyria (EU 2014, US 2019). The two molecules differ in structure (cyclic vs. linear), in receptor pharmacology (non-selective vs. MC1R-selective), and in regulatory status (MT-2 is not approved for any indication).

Is MT-2 the same as an MC4R-preferring melanocortin analog?

No. an MC4R-preferring melanocortin analog is a separate, structurally and pharmacologically distinct linear melanocortin-agonist peptide that is MC4R-preferring and that has been approved for a specific sexual-function indication. MT-2 is a cyclic non-selective compound that is not an MC4R-preferring melanocortin analog and is not approved for any indication.

What is the structure of MT-2?

MT-2 is a cyclic heptapeptide with sequence Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-NH2. The cyclization is via a lactam bridge between the Asp side chain and the Lys side chain. The N-terminus is acetylated and the C-terminus is amide-capped. The molecular weight is approximately 1024 g/mol. The key structural features are the D-phenylalanine substitution at position 7 (a potency-enhancing modification in melanocortin-agonist chemistry) and the lactam cyclization that constrains the conformation.

What are the melanocortin receptors?

The melanocortin receptors are a family of five G-protein-coupled receptors (MC1R through MC5R) that signal through Gαs and cyclic AMP. MC1R is principally expressed in melanocytes (pigmentation). MC2R is the ACTH receptor in the adrenal cortex (cortisol release). MC3R and MC4R are expressed in CNS sites and are involved in energy homeostasis and other functions; loss-of-function MC4R variants are the most common monogenic cause of human obesity. MC5R is expressed in exocrine glands and peripheral tissues.

Why is MT-2 a research compound only?

MT-2 was developed as a research-pharmacology tool and as a structural template for subsequent receptor-subtype-selective melanocortin-agonist development. The clinical development of melanocortin agonists has generally favored receptor-subtype-selective compounds (afamelanotide for MC1R, an MC4R-preferring melanocortin analog for MC4R, setmelanotide for MC4R) rather than the broad non-selective profile of MT-2. MT-2 is not approved for any indication and is supplied as a research-supply peptide for laboratory melanocortin-pharmacology research.

What is the difference between MT-2 and α-MSH?

α-MSH is the endogenous 13-amino-acid melanocortin peptide produced by post-translational processing of pro-opiomelanocortin (POMC). MT-2 is a cyclic synthetic 7-amino-acid analog with structural modifications (N-terminal acetylation, Nle replacement of Met, D-Phe substitution at position 7, lactam cyclization) that confer high potency, broad melanocortin-receptor agonist activity, and substantial resistance to proteolytic degradation. MT-2 is much more potent and much more metabolically stable than the parent α-MSH.

Why is the D-phenylalanine substitution important?

Replacement of the natural L-phenylalanine at position 7 of α-MSH with D-phenylalanine is the single most important potency-enhancing modification in melanocortin-agonist medicinal chemistry. The chirality inversion at this central pharmacophore residue substantially increases receptor-binding affinity and functional potency across the melanocortin receptor subtypes. The substitution was identified through systematic structure-activity work in the Hadley/Hruby laboratories and is used in MT-2 and in essentially all subsequent receptor-subtype-selective melanocortin agonists derived from the α-MSH active core.

What is the role of the lactam cyclization?

The lactam bridge between the Asp⁵ side chain and the Lys¹⁰ side chain in MT-2 constrains the conformation of the central His-D-Phe-Arg-Trp pharmacophore, rigidifying the bioactive conformation and increasing receptor-binding affinity by reducing the entropic cost of receptor engagement. The cyclization also provides substantial resistance to proteolytic degradation by removing accessible exopeptidase and endopeptidase cleavage sites in the central peptide region. This cyclization is a defining feature of MT-2 relative to the linear Melanotan-1 (afamelanotide).

Has MT-2 been studied in obesity research?

Yes. Because MT-2 is an agonist at MC4R — the principal melanocortin receptor mediating CNS effects on food intake and energy expenditure, and the receptor whose loss-of-function in humans is the most common monogenic cause of obesity — MT-2 has been used in preclinical rodent research investigating melanocortin effects on feeding behavior, body weight, and energy expenditure. The MC4R-selective compound setmelanotide is a downstream clinical translation of melanocortin-MC4R pharmacology for syndromic obesity.

Has MT-2 been studied in erectile function research?

Yes. MC4R agonism has effects on erectile function through CNS melanocortin signaling, and MT-2 (a non-selective melanocortin agonist that engages MC4R) has been used in preclinical research investigating these effects. The downstream clinical translation of MC4R-erectile pharmacology produced an MC4R-preferring melanocortin analog (an MC4R-preferring compound) as an approved medicine for a specific sexual-function indication. MT-2 is not an MC4R-preferring melanocortin analog and is not an approved medicine for any sexual-function or any other indication.

What is the role of MT-2 in melanocortin receptor binding assays?

MT-2 (and the closely related linear NDP-α-MSH / Melanotan-1) is widely used as a reference agonist in melanocortin receptor radioligand-binding assays. The [125I]NDP-α-MSH radiotracer is the standard radioligand for MC1R, MC3R, MC4R, and MC5R binding studies, and MT-2 is used as a non-radioactive reference agonist for displacement and functional assays. Its non-selective potency profile across the receptor subtypes makes it useful as a broadly applicable reference compound in this work.

How is research-supply MT-2 stored?

Research-supply MT-2 is supplied as a sterile lyophilized peptide in a sealed vial. Lyophilized storage is at -20 °C or below in a moisture-protected container. Reconstituted solutions in aqueous diluent (typically bacteriostatic water) are stored refrigerated (2-8 °C) and used within a short window per standard peptide-stability practice. The cyclized peptide has good solid-state stability and good solution stability under appropriate storage conditions.

What regulatory advisories have been issued for non-research use of MT-2?

Several regulatory authorities including the UK Medicines and Healthcare products Regulatory Agency (MHRA), the Australian Therapeutic Goods Administration (TGA), and the US FDA have issued advisories regarding non-research, non-medical use of Melanotan-1 and Melanotan-2 in contexts such as skin tanning, citing safety concerns including unmonitored receptor effects, suspect product quality in non-research supply channels, and unknown long-term consequences. These advisories are publicly available from the respective regulators. The research-supply context of this page is academic and laboratory melanocortin-pharmacology research only.

MT-2 (Melanotan 2) (with Bacteriostatic Water) lyophilized vial with bacteriostatic water for research

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MT-2 (Melanotan 2) (with Bacteriostatic Water)

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MT-2 (Melanotan II) is a synthetic peptide analog of alpha-melanocyte stimulating hormone (α-MSH) that is widely studied in melanocortin receptor research, pigmentation biology, and appetite signaling pathways. It is a potent research compound used in preclinical studies involving melanogenesis, energy balance, and neuroendocrine signaling. This compound is manufactured to strict laboratory-grade standards and is intended strictly for qualified scientific and preclinical research use only.

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