PT-141 (Bremelanotide) 10 mg: Melanocortin Receptor Research Peptide

PT-141 is a seven-residue peptide that is cyclized through a lactam bridge between the side chains of an aspartic acid and a lysine residue. Its sequence is commonly written as Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, with an N-terminal acetyl group, a norleucine (Nle) residue in place of methionine, and a D-phenylalanine within the ring.

The molecular formula is C₅₀H₆₈N₁₄O₁₀, corresponding to a molecular weight of approximately 1025.2 g/mol. Because it carries a free C-terminal carboxylic acid, PT-141 differs from the closely related cyclic analog melanotan II, which carries a C-terminal amide. Both compounds were developed from structure–activity work on the melanocortin peptide family.

α-MSH is an endogenous 13-residue peptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂) produced by post-translational processing of the precursor pro-opiomelanocortin (POMC). The core tetrapeptide His-Phe-Arg-Trp is the shared pharmacophore that melanocortin receptors recognize.

PT-141 retains this His-Phe-Arg-Trp motif but makes several changes that are typical of melanocortin analog design:

• Cyclization constrains the backbone into a turn conformation around the pharmacophore and increases resistance to proteolysis compared with the linear parent peptide.
• D-Phe substitution in place of L-Phe is a classic modification in melanocortin chemistry that increases receptor potency.
• Norleucine replaces methionine, removing an oxidation-prone thioether side chain.
• Truncation removes the N- and C-terminal residues of α-MSH that are not required for receptor activation.

These features make PT-141 a compact, conformationally constrained tool compound for probing how the melanocortin pharmacophore interacts with its receptors.

The melanocortin system comprises five G protein-coupled receptors, MC1R through MC5R. All five couple predominantly to G_s, so agonist binding stimulates adenylyl cyclase and raises intracellular cAMP. The receptors differ in tissue distribution and ligand preference:

• MC1R is expressed on melanocytes and responds strongly to α-MSH.
• MC2R is the adrenocorticotropic hormone (ACTH) receptor and requires the accessory protein MRAP for trafficking; it is not activated by α-MSH.
• MC3R and MC4R are expressed widely in the central nervous system, including hypothalamic nuclei, and are the subtypes most frequently studied with PT-141.
• MC5R is found in exocrine glands and several peripheral tissues.

MC3R and MC4R are also regulated by an endogenous antagonist/inverse agonist, agouti-related protein (AgRP), which makes them a well-characterized model for studying how agonists and inverse agonists compete at the same GPCR.

In receptor pharmacology studies, PT-141 behaves as a nonselective melanocortin agonist: it activates several melanocortin receptor subtypes rather than a single one, with MC3R and MC4R the most commonly investigated. Typical in vitro readouts include:

• cAMP accumulation in cell lines engineered to express a single receptor subtype, used to generate concentration–response curves and EC₅₀ values.
• Radioligand or fluorescent ligand competition binding, often against labeled NDP-α-MSH, to estimate affinity.
• β-arrestin recruitment and receptor internalization assays to examine signaling bias and desensitization.
• Competition with AgRP to study inverse agonism and constitutive receptor activity at MC4R.

Because PT-141 is cyclic and protease-resistant, it is useful as a stable reference agonist when comparing new linear or cyclic melanocortin ligands. Researchers using it as a comparator usually run it alongside α-MSH or NDP-α-MSH to anchor potency measurements across experiments.

Each lot of PT-141 10 mg research material should be supported by documentation that confirms identity, purity and quantity:

• Reversed-phase HPLC purity, reported as the area percentage of the main peak at a stated UV wavelength.
• Mass spectrometry (ESI or MALDI) showing an observed mass consistent with the theoretical value of about 1025 Da.
• Fill weight per vial, stated as 10 mg of lyophilized peptide.
• Appearance, typically a white to off-white lyophilized solid.

A certificate of analysis (COA) ties these results to a specific lot number so that data generated in the laboratory can be traced back to the material used.

Lyophilized PT-141 is generally stored sealed, protected from light and moisture, at −20 °C for long-term storage. Before opening, vials should be allowed to reach room temperature to limit condensation, since lyophilized peptides are hygroscopic. Once dissolved, stock solutions are best divided into single-use aliquots and kept frozen, avoiding repeated freezing and thawing. For general guidance on preparing stock solutions, see our article on preparing lyophilized peptide solutions for laboratory assays.

NuRev supplies PT-141 for laboratory research use only; it is not for human or veterinary use.