Key findings
- One of four high resolution structures of full-length melanocortin-4 receptor in complex with heterotrimeric Gs protein was obtained with this peptide as the stimulating ligand, alongside alpha-MSH, afamelanotide and a small molecule. [1]
- Forced degradation under acidic, basic, neutral hydrolytic, oxidative, thermal and photolytic stress produced eight degradation products, with deacetylation, peptide bond hydrolysis, oxidation and epimerization as the major pathways. [2]
- In human glioblastoma cell lines the peptide reduced survivin expression and induced cell death, and an antagonist of melanocortin receptors 3 and 4 cancelled both effects. [3]
- High resolution Orbitrap mass spectrometry established elemental composition and structural features for seized samples labeled as this peptide and as melanotan II, without reference standards for either. [4]
Identity and structure
- Class
- A cyclic peptide of the melanocortin family, grouped with setmelanotide as a macrocyclic peptide [2][5]
- Receptors in cited work
- Melanocortin receptors 3 and 4; an antagonist of both cancelled the cellular effect observed in glioblastoma lines [3]
- Structural record
- Resolved as the stimulating ligand in a full-length melanocortin-4 receptor and Gs protein complex [1]
- Distinct from melanotan II
- The two were characterised as separate compounds by accurate mass and fragmentation in the cited mass spectrometry work [4]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The receptor structures place the peptidic agonists in a conserved binding mode and contrast that with the distinctive details of small molecule recognition, which the authors link to receptor subtype selectivity and to an activation mechanism particular to melanocortin-4 receptor. [1]
Cellular work supports receptor mediation rather than a direct cytotoxic action. Both the fall in survivin and the cell death were cancelled by an antagonist of melanocortin receptors 3 and 4, and forced over-expression of survivin prevented the cell death on its own. [3]
Research findings
Structural
- System
- Four high resolution structures of full-length melanocortin-4 receptor in complex with heterotrimeric Gs protein, stimulated separately by alpha-MSH, afamelanotide, this peptide and the small molecule THIQ, with accompanying pharmacological assays
- Measured
- Ligand binding mode, receptor activation features and G protein coupling
- Reported
- The peptidic agonists share a conserved binding mode. Small molecule recognition differs in molecular detail, which the authors relate to receptor subtype selectivity, and the receptor shows an activation mechanism distinct from other melanocortin receptor family members. [1]
Analytical
- System
- Bremelanotide acetate held under acidic, basic, neutral hydrolytic, oxidative, thermal and photolytic stress, analysed by a stability indicating reversed phase HPLC method and by liquid chromatography high resolution tandem mass spectrometry with computational modelling
- Measured
- Method linearity, precision and accuracy; number and identity of degradation products; probable stereochemical sites of epimerization
- Reported
- Linearity ran from 25 to 150 micrograms per mL with a coefficient of determination of 0.9993. Degradation was lower under acidic than basic conditions and marked under oxidative conditions, with further loss under thermal and photolytic stress. Eight degradation products were detected and characterised, and the major pathways were deacetylation, peptide bond hydrolysis, oxidation and epimerization. [2]
In vitro
- System
- Human glioblastoma cell lines, alone or combined with chemotherapeutic agents, and with an antagonist of melanocortin receptors 3 and 4 or forced survivin over-expression
- Measured
- Survivin expression and cell viability
- Reported
- Survivin expression fell and cell death rose at concentrations that were not toxic to normal human cells. The melanocortin receptor 3 and 4 antagonist cancelled both effects, and forced survivin over-expression prevented the cell death. The peptide also promoted cell death induced by temozolomide and osimertinib. [3]
Analytical
- System
- Eight unknown confiscated samples characterised by liquid chromatography and high resolution Orbitrap mass spectrometry without reference standards
- Measured
- Accurate mass of the protonated species, isotopic patterns and relative isotopic abundance, accurate mass of collision-induced product ions
- Reported
- The approach established the elemental composition and structural characteristics of both compounds, melanotan II and bremelanotide, in samples for which no reference standard was available. [4]
In vitro
- System
- Fourteen macrocyclic peptide analogues of 19 to 23 membered rings built on MT-II, SHU-9119 and PG-901 scaffolds, profiled at human melanocortin receptors 1, 3, 4 and 5; the tested compounds are analogues rather than the catalog peptide
- Measured
- Agonist and antagonist activity and selectivity across the four human receptors
- Reported
- Two of the analogues emerged as potent and selective antagonists at human melanocortin-4 receptor, and a third showed agonist activity with marked selectivity for the same receptor. [5]
Handling for in-vitro work
- Stability in cited work
- Degradation was greater under basic than acidic conditions and marked under oxidative, thermal and photolytic stress [2]
- Storage
- Lyophilized material kept at minus 20 degrees C, dark, dry and protected from light; reconstituted aliquots kept cold and used promptly
Open questions
- No cited study reports binding constants for this peptide across melanocortin receptors 1, 3, 4 and 5 in a single panel, so its selectivity profile is not quantified by this set.
- The eight degradation products were characterised from deliberately stressed material rather than from stored vials, so how quickly a lyophilized lot accumulates them is not established here.
A clinical literature exists for this peptide as a finished pharmaceutical formulation. It is out of scope for a research material profile and none of it is summarized here.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0021-1 ↗PT-141 · 99.40% HPLC2026-09-16
References
- Zhang H, Chen LN, Yang D, et al. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell research. 2021.
- Yuvaraaj VK, Sharma N Comprehensive characterization of bremelanotide acetate and its degradants by LC-HRMS/MS and predicting epimerization through computational modelling. Analytical methods : advancing methods and applications. 2026.
- Suzuki S, Kitanaka C, Okada M Melanocortin Receptor Agonist Bremelanotide Induces Cell Death and Growth Inhibition in Glioblastoma Cells via Suppression of Survivin Expression. Anticancer research. 2024.
- Mestria S, Odoardi S, Frison G, et al. LC-HRMS characterization of the skin pigmentation and sexual enhancers melanotan II and bremelanotide sold on the black market of performance and image enhancing drugs. Drug testing and analysis. 2021.
- Merlino F, Jia L, Boccino I, et al. Goldilocks-Inspired Design of Mid-Size Macrocycles for Selective Targeting of Human Melanocortin Receptors. Journal of medicinal chemistry. 2026.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.