PT-141 10mg

What is PT-141 ?

PT-141 (bremelanotide, also written PT141 or PT 141) prefers MC4R over the other melanocortin receptors by a wide margin. It is supplied as a 10mg lyophilised powder.

Its sequence is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. A lactam bridge joins the aspartate side chain at position 5 to the lysine side chain at position 10. Norleucine replaces the oxidation-prone methionine of native alpha-MSH at position 4, and D-phenylalanine sits at position 7 inside the His-Phe-Arg-Trp core. PT-141 differs from Melanotan II only at the C-terminus, where a free carboxylic acid replaces the primary amide. In other words, PT-141 is the free-acid form of Melanotan II.

PT-141 Research Applications

• Subtype-ratio work : PT-141 and Melanotan II differ at one terminal group, a clean test of how C-terminal charge redistributes affinity across MC1R, MC3R, MC4R and MC5R.
• Structural biology : Zhang et al. (Cell Res, 2021) resolved bremelanotide bound to full-length MC4R in complex with Gs, alongside alpha-MSH, afamelanotide and a small-molecule agonist.
• Analytical methods : bremelanotide is a test analyte for cyclic-peptide quantification by UHPLC-MS/MS.

PT-141 is used in vitro as an MC4R-preferring reference agonist at the human melanocortin receptors. All five subtypes are class A G-protein-coupled receptors signalling mainly through Gs and adenylyl cyclase. This is receptor-level and analytical work, not evidence of any effect in humans.

PT-141 vs Melanotan II vs Melanotan I

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 the same ring with a free acid at the C-terminus (C₅₀H₆₈N₁₄O₁₀, 1025.2 g/mol, CAS 189691-06-3). The difference is one nitrogen for one oxygen, about 1 Da. The receptor profiles still diverge. Melanotan II has comparable potency at MC1R and MC4R and only modestly less at MC3R and MC5R, so it serves as the flat positive-control agonist. PT-141 prefers MC4R over every other subtype.

Melanotan I, a linear tridecapeptide (1646.9 g/mol, CAS 75921-69-6), is MC1R-weighted by about an order of magnitude. Small chemical changes move the subtype ratios, so substituting one for another invalidates a comparison. None of the three is active at MC2R, the adrenocorticotropin receptor.

Research Overview

PT-141, also indexed as bremelanotide, is a cyclic lactam heptapeptide analogue of alpha-melanocyte-stimulating hormone with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH (C₅₀H₆₈N₁₄O₁₀, 1025.2 g/mol, CAS 189691-06-3). Structurally it differs from Melanotan II at a single terminal position: where Melanotan II ends in a primary carboxamide, PT-141 ends in a free carboxylic acid, and it is described in the analytical literature as the deamidation product of that parent molecule. Everything else is shared, 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, 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. That one C-terminal change has a disproportionate pharmacological consequence, which is why PT-141 and Melanotan II should never be substituted for one another in a protocol. Melanotan II is essentially flat across four receptor subtypes. In a single internally consistent radioligand series measuring inhibition of ¹²⁵I-NDP-alpha-MSH binding to membranes from BHK570 cells stably expressing each human receptor, bremelanotide returned Ki values of 0.25 nM at MC4R, 6.4 nM at MC1R, 17 nM at MC5R and 53 nM at MC3R, corresponding to pKi 9.6, 8.2, 7.8 and 7.3 respectively. Expressed as ratios within that dataset, this is roughly 26-fold preference for MC4R over MC1R, 68-fold over MC5R and 210-fold over MC3R, with no value reported at MC2R, the adrenocorticotropin receptor, which alpha-MSH analogues of this class do not engage. All melanocortin receptors are class A G-protein-coupled receptors signalling principally through Gs and adenylyl cyclase to raise intracellular cAMP, and MC4R is the subtype whose ligand-bound active-state architecture is best resolved, including a 2021 cryo-EM series that captured bremelanotide bound to full-length MC4R in complex with heterotrimeric Gs. 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.

Storage and Reconstitution

Store PT-141 powder sealed at -20°C in the dark. Keep reconstituted solution refrigerated at 2-8°C in amber or foil-wrapped vessels. Tryptophan oxidation is the main degradation route, with histidine a secondary site. Freeze-thaw cycles speed aggregation and oxidation, so freeze single-use aliquots.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

Let the vial reach room temperature. Run bacteriostatic water slowly down the inside wall of the vial and swirl gently until dissolved, without shaking. Work away from direct sunlight and fluorescent light, because tryptophan 9 is photolabile. The free C-terminal carboxylate carries an extra negative charge at neutral pH, so record buffer pH when comparing PT-141 with Melanotan II in one assay.

• Protect from light at all stages. Tryptophan at position 9 is the photolabile residue and its oxidation is the degradation route most commonly detected by RP-HPLC in stored melanocortin analogues, with histidine a secondary site of concern.
• Unlike the C-terminal amide of Melanotan II, the free carboxylate here is titratable and carries an additional negative charge at neutral pH, so record buffer pH alongside concentration when comparing the two molecules in the same assay.
• Aliquot into amber or foil-wrapped single-use vessels and avoid repeated freeze-thaw cycling, which accelerates both aggregation and oxidative degradation. The single tryptophan residue gives a usable chromophore, so concentration can be verified by UV absorbance at 280 nm where assay design requires it.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

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)

Published research on PT-141 is indexed on PubMed. See our full UK buyer's guide for PT-141 and UK buyer's guide for PT-141 CoA.