PT-141

What is PT-141?

PT-141 is a synthetic cyclic lactam heptapeptide analogue of alpha-melanocyte-stimulating hormone, sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH (C₅₀H₆₈N₁₄O₁₀, 1025.2 g/mol, CAS 189691-06-3), and its international non-proprietary name is bremelanotide. The scaffold is a 23-membered macrocycle closed by a lactam bridge between the aspartate side-chain carboxyl at position 5 and the lysine side-chain amine at position 10, with norleucine at position 4 in place of the oxidation-prone methionine of the native hormone and D-phenylalanine at position 7 inside the conserved His-Phe-Arg-Trp message core. It differs from Melanotan II only at the C-terminus, where a primary carboxamide is replaced by a free carboxylic acid, and it is described in the analytical literature as the deamidation product of that parent molecule. Pharmacologically it is a melanocortin receptor agonist with a marked preference for MC4R. Bremelanotide is authorised as a medicine in the United States. The material supplied here is not a medicine, holds no UK marketing authorisation, and is supplied as lyophilised powder strictly for in-vitro laboratory research use only, not for human or veterinary administration.

PT-141 vs Melanotan II vs Melanotan I

PT-141 and Melanotan II are the closest pair in the melanocortin catalogue and the pair most often conflated, which makes the distinction worth stating precisely. Melanotan II is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂ (C₅₀H₆₉N₁₅O₉, 1024.2 g/mol, CAS 121062-08-6). PT-141 is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH (C₅₀H₆₈N₁₄O₁₀, 1025.2 g/mol, CAS 189691-06-3). One nitrogen for one oxygen, about 1 Da, identical macrocycle, identical bridge, identical stereochemistry at position 7. Despite that, the subtype profiles diverge sharply. Melanotan II is essentially non-selective, with comparable potency at MC1R and MC4R and only modestly less at MC3R and MC5R, which is exactly why it is used as the flat positive-control agonist. PT-141, measured in a single radioligand displacement series against ¹²⁵I-NDP-alpha-MSH on membranes from BHK570 cells stably expressing each human subtype, returned Ki 0.25 nM at MC4R, 6.4 nM at MC1R, 17 nM at MC5R and 53 nM at MC3R, roughly 26-fold, 68-fold and 210-fold preference for MC4R over MC1R, MC5R and MC3R respectively. Melanotan I sits at the other end of the range: a linear tridecapeptide (C₇₈H₁₁₁N₂₁O₁₉, 1646.9 g/mol, CAS 75921-69-6) that is MC1R-weighted by about an order of magnitude. Read together, the three illustrate how little chemistry it takes to move a melanocortin ligand's subtype ratios, and why substituting one for another in a protocol invalidates the comparison. None of them is active at MC2R, the adrenocorticotropin receptor.

PT-141 Research Applications

PT-141 is used in vitro as an MC4R-preferring reference agonist at the human melanocortin receptors, and as a structure-activity probe of the C-terminus. The five subtypes are class A G-protein-coupled receptors signalling principally through Gs and adenylyl cyclase to raise intracellular cAMP, and the conserved His-Phe-Arg-Trp core of alpha-MSH is the message sequence recognised by the orthosteric pocket. Three research contexts recur in the literature. First, subtype-ratio work: because PT-141 and Melanotan II are identical apart from one terminal group, the pair is a clean test case for how charge and hydrogen-bonding capacity at the C-terminus redistribute affinity across MC1R, MC3R, MC4R and MC5R, with the quantitative anchor being the 2012 J Med Chem radioligand series that measured all four subtypes under one assay format. Second, structural biology: cryo-EM structures of full-length MC4R in complex with heterotrimeric Gs, published in Cell Research in 2021, resolved bremelanotide in the orthosteric site alongside alpha-MSH, afamelanotide and a small-molecule agonist, establishing a conserved binding mode for the peptidic ligands and a distinct activation mechanism for MC4R. Third, analytical method development, where bremelanotide is a demanding test analyte for cyclic-peptide quantification and UHPLC-MS/MS assays have been published at sub-nanogram sensitivity. All of this is receptor-level and analytical characterisation in recombinant systems and instrumentation, not evidence of any effect in humans.

Reconstitution Guide

Allow vials to reach room temperature, then sterilise the rubber stopper of both the peptide vial and the bacteriostatic water vial with an alcohol swab. Slowly draw your bacteriostatic water into a sterile insulin syringe, then inject it gently down the inner glass wall of the peptide vial, never directly onto the lyophilised powder. Once added, gently swirl the vial in a slow circular motion until fully dissolved. Never shake or vortex. The solution should be clear and colourless. Label the vial with the reconstitution date and store immediately. PT-141 is photolabile, principally through oxidation of the tryptophan residue at position 9, so reconstitute away from direct sunlight and fluorescent lighting and transfer aliquots into amber or foil-wrapped vessels. Unlike the C-terminal amide of Melanotan II, the free carboxylate is titratable and carries an additional negative charge at neutral pH, so record buffer composition and pH alongside concentration if the two molecules are being compared in the same assay. The single tryptophan residue gives a usable chromophore, so concentration can be verified by UV absorbance at 280 nm where assay design requires it.

See our full peptide reconstitution guide and reconstitution calculator for step-by-step protocol.

Storage Instructions

Lyophilised vials should be stored at -20°C, protected from light and moisture, and remain stable for up to 24 months. Once reconstituted with bacteriostatic water, store the solution at 2-8°C (standard refrigerator) and use within approximately 3 months. For storage beyond that, prepare single-use aliquots at -20°C, where reconstituted peptide remains stable for up to 6 months. Avoid repeated freeze-thaw cycles and always handle under sterile laboratory conditions. PT-141 should be kept protected from UV and fluorescent light in both lyophilised and reconstituted form. Tryptophan oxidation is the degradation route most commonly detected by RP-HPLC in stored melanocortin analogues, with histidine a secondary site of concern, and freeze-thaw cycling accelerates both aggregation and oxidative degradation. Prepare single-use aliquots rather than repeatedly accessing one stock vial.

Frequently Asked Questions

Research References

• Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective alpha-melanocyte-stimulating hormone (alpha-MSH) analogues (J Med Chem, 2012)
• Structural insights into ligand recognition and activation of the melanocortin-4 receptor (Cell Res, 2021)
• Ultra-sensitive quantification of the cyclic peptide bremelanotide utilizing UHPLC-MS/MS (J Pharm Biomed Anal, 2020)

Related Research Compounds

• → Melanotan II 10mg
• → Melanotan I 10mg
• → Bacteriostatic Water 10ml