Melanotan 2 (Cyclic Heptapeptide Lactam)

DISCLAIMER: For Research Use Only (RUO). Not for human or veterinary use. Not for cosmetic application.

Melanotan II (MT-II) is a synthetic cyclic heptapeptide engineered to act as a potent, non-selective agonist of the melanocortin peptide receptor family (MC1R, MC3R, MC4R, MC5R). Unlike the linear endogenous hormone α-MSH, Melanotan II utilizes a lactam bridge cyclization to enhance enzymatic stability and receptor binding affinity. It is supplied strictly for laboratory investigation into melanogenesis signaling, central nervous system (CNS) arousal pathways, and metabolic regulation. As a compound classified in FDA 503A Category 2 (Significant Safety Risks), it is intended solely for controlled in vitro and in vivo animal model research.

Product Specifications

Description

Melanotan 2 is a superpotent melanocortin analog developed to overcome the rapid enzymatic degradation of natural α-MSH. Through rational drug design, the inclusion of D-Phenylalanine (D-Phe) at position 7 and the formation of a covalent lactam bridge between Aspartic Acid (residue 5) and Lysine (residue 10) constrain the peptide into a rigid beta-turn conformation.

This structural modification significantly increases its binding affinity (Ki) across multiple melanocortin receptor subtypes, specifically MC1R (pigmentation) and MC4R (energy homeostasis and neuro-signaling).

In the research context, Melanotan 2 serves as a critical probe for mapping the central melanocortin system. It is extensively utilized to study the pathophysiology of energy balance, the regulation of tyrosinase activity in melanocytes, and the hemodynamic effects of sympathomimetic activation. Due to its ability to cross the blood-brain barrier in animal models, it remains a primary tool for investigating neuro-mediated physiological responses.

Experimental & Analytical Use

Melanotan 2 is utilized in laboratory research for several primary applications:

• Receptor Kinetics: Determining binding constants (Ki) and signal transduction efficacy at MC1R vs. MC4R interfaces.

• Metabolic Signaling: Investigating lipolysis and appetite suppression pathways in rodent obesity models.

• Toxicology Modeling: Studying the mechanisms of sympathomimetic toxicity, renal vasoconstriction, and rhabdomyolysis in high-dose scenarios.

• Neurophysiology: Exploring the role of MC4R activation in CNS arousal and thermoregulation.

• Analytical Calibration: Serving as a reference standard for LC-MS/MS detection of peptide impurities and metabolites in forensic toxicology.

Toxicology and Detection Methods

For forensic and anti-doping research, Melanotan 2 is identified in biological matrices using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

• Primary Analyte: The intact parent peptide is monitored using the doubly charged precursor ion $[M+2H]^{2+}$ at m/z 513.

• Metabolite Profile: Research indicates Melanotan 2 resists rapid hydrolysis due to the lactam bridge, but metabolites resulting from deamidation and C-terminal cleavage can be detected.

• Adverse Event Mechanisms: Investigational models use MT-II to study renal infarction pathways, specifically hypothesizing that non-selective MCR activation triggers severe sympathetic vasoconstriction and thrombotic microangiopathy in renal vasculature.

(Note: These analytical methods are used exclusively for forensic, anti-doping, and laboratory toxicology research.)

Handling and Stability

Melanotan 2 is supplied as a lyophilized white powder (acetate salt).

• Reconstitution: Soluble in sterile bacteriostatic water. However, for extended stability during assays, reconstitution in dilute acetic acid (0.1%) is often preferred to prevent base-catalyzed deamidation.

• Lactam Bridge Sensitivity: While the cyclic structure confers serum stability, the peptide is sensitive to hydrolysis at extreme pH. Avoid repeated freeze-thaw cycles which can disrupt conformational integrity.

• Storage Instructions:

  • Store lyophilized vials in a sealed container at -20°C.

  • Protect from UV light and moisture.

  • Reconstituted aliquots should be used immediately or stored at -80°C.

  • Maintain strictly within an RUO-standard laboratory environment.

Molecular & Technical Characteristics

Synthesized using Solid Phase Peptide Synthesis (SPPS), Profound Aminos' Melanotan 2 is purified to eliminate synthesis-related impurities:

• Stereochemical Purity: Rigorous testing ensures the D-Phe7 residue has not racemized during synthesis, which would otherwise alter receptor selectivity.

• Impurity Profile: Complete elimination of "failure sequences" and aspartimide byproducts frequently found in lower-grade preparations.

• Stability: The N-acetyl and C-amidated termini provide resistance to exopeptidases, making it highly suitable for prolonged in vivo animal studies compared to linear peptides.

Scientific Significance

The study of Melanotan 2 contributes to the broader understanding of:

• GPCR Pharmacology: Ligand-receptor interaction dynamics of Class A G-Protein Coupled Receptors.

• Sympathetic Nervous System: The role of melanocortins in blood pressure regulation and renal hemodynamics.

• Immunogenicity: The FDA has flagged Melanotan 2 for potential immunogenicity risks (development of anti-drug antibodies) due to peptide aggregation, making it a subject of interest for immunological safety research.

RUO Compliance & Regulatory Status

All experimental applications of Melanotan 2 must be conducted under Research Use Only (RUO) protocols.

• FDA Status: Placed on the 503A Bulks List Category 2 (Significant Safety Risks) as of late 2023/2024. It is strictly prohibited for use in compounding for human administration.

• WADA Status: Explicitly prohibited under Section S2 (Peptide Hormones).

• Intended Use: Not for diagnostic, therapeutic, cosmetic, or veterinary purposes.

Features / Highlights

• Potent, non-selective agonist of MC1R, MC3R, MC4R, and MC5R.

• Cyclic heptapeptide structure with verified lactam bridge integrity.

• Enables investigation into sympathomimetic toxicity and renal pathophysiology.

• Verified ≥98% purity via HPLC to minimize D-Phe7 racemization.

• High stability profile compared to linear α-MSH.

• Strictly designed and labeled for Research Use Only (RUO).

Why Profound Aminos?

Profound Aminos supplies high-purity Melanotan 2 (Acetate) for controlled pharmacological, toxicological, and receptor-binding research programs. Researchers value our commitment to quality through:

1. Stereochemical Validation: RUO-grade Melanotan 2 with verified D-Phenylalanine integrity ensures accurate receptor binding data (Ki).

2. Impurity Transparency: Rigorous removal of synthesis byproducts that can skew immunogenicity and toxicity assays.

3. Mass Spec Verification: Identity confirmation matching the specific cyclic mass (1024.2 Da) detects potential ring-opening degradation.

4. Regulatory Awareness: Clear documentation and labeling align with FDA 503A Category 2 safety advisories.

Profound Aminos is the trusted choice for research organizations studying melanocortin signaling, renal hemodynamics, and peptide toxicology.

Frequently Asked Questions (FAQs)

Q1: What is the primary research application of Melanotan 2?

Melanotan 2 is used to investigate the signaling pathways of melanocortin receptors (MC1R-MC5R), specifically studying effects on energy homeostasis, CNS arousal, and melanogenesis in animal models.

Q2: How does Melanotan 2 differ from Melanotan I?

Melanotan 2 is a cyclic heptapeptide with a lactam bridge and non-selective binding affinity (including MC4R), whereas Melanotan I is a linear peptide with higher selectivity primarily for MC1R.

Q3: Why is Melanotan 2 listed as an FDA Category 2 substance?

The FDA placed Melanotan 2 in Category 2 due to significant safety risks identified in research, including immunogenicity (immune reaction to the peptide) and the potential for renal and cardiovascular toxicity.

Q4: How should Melanotan 2 be stored for optimal stability?

It should be stored as a lyophilized powder at -20°C. Once reconstituted, the lactam bridge can degrade over time; therefore, immediate use or storage at -80°C is highly recommended.

Q5: Is Melanotan 2 suitable for human use?

No. Melanotan 2 is strictly for Research Use Only (RUO) and is not approved for human consumption, cosmetic tanning, or therapeutic use.

References

1. Nelson ME, Bryant SM, Aks SE. Melanotan 2 injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-1173.

2. U.S. Food and Drug Administration (FDA). Pharmacy Compounding Advisory Committee (PCAC) Briefing Document: Melanotan 2. FDA.gov. Published October 2024. Accessed December 2025.

3. Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan 2: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020;9(2):159-161. doi:10.1007/s13730-020-00447-z.

4. World Anti-Doping Agency (WADA). The 2025 Prohibited List: International Standard. Section S2: Peptide Hormones, Growth Factors, Related Substances, and Mimetics. WADA-ama.org. Effective January 1, 2025.

5. Breindahl T, Evans-Brown M, Hindersson P, et al. Identification and characterization by LC-UV-MS/MS of melanotan 2 skin-tanning products sold illegally on the Internet. Drug Test Anal. 2015;7(2):164-172.

6. Hadley ME, Hruby VJ, Blanchard J, et al. Discovery and development of novel melanogenic drugs. Melanotan-I and -II. Pharm Biotechnol. 1998;11:575-595.

7. Dorr RT, Lines R, Levine N, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-1784.

8. Vanhee C, Janvier S, Desmedt B, et al. Analysis of illegal peptide biopharmaceuticals: Amino acid analysis and active pharmaceutical ingredient (API) identification. Talanta. 2015;144:63-70.

9. Navarro M, Cubero I, Chen AS, et al. Effects of Melanotan-II, a melanocortin agonist, on ethanol intake and neurochemistry in P rats. Pharmacol Biochem Behav. 2002;72:149.

RUO DISCLAIMER: This compound is for Research Use Only (RUO). It is not intended for human, veterinary, or cosmetic applications. All information provided is based on peer-reviewed scientific literature and intended solely for laboratory and academic research purposes. This product is not a dietary supplement or drug.