Everything below reports findings from cell cultures, isolated tissue and animals. This material is for research use only, not for human or veterinary use.
Few research peptides sit in a published receptor structure. PT-141 does. A 2021 cryo-electron microscopy study captured the full-length human melanocortin-4 receptor coupled to its G protein, with bremelanotide occupying the orthosteric pocket (PMID 34433901) [1]. The binding pose is resolved at atomic scale.
The behavioural mechanism is not. A 2025 study built specifically to trace how the peptide acts on the mesolimbic dopamine system found no change in melanocortin receptor expression and no enhancement of the reward measure it used (PMID 39793696) [2].
That gap defines the compound. Chemistry and receptor engagement are settled. The circuit-level account remains an active question. That is what makes PT-141 useful as a reference agonist rather than a finished story.
Indexed human papers exist. Those human endpoints sit outside this profile. The useful laboratory questions are sequence, the one-atom difference from melanotan II, the receptor pose, and what the hamster work actually measured.
Chemical identity
A cyclic heptapeptide built on the alpha-melanocyte-stimulating hormone core, closed by a lactam bridge between two side chains.
| Property | Value |
|---|---|
| Sequence | Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH |
| Common names | PT-141, bremelanotide, PT-14 |
| Molecular formula | C50H68N14O10 |
| Molecular weight | 1025.2 |
| CAS | 189691-06-3 |
| PubChem CID | 9941379 |
| InChIKey | FFHBJDQSGDNCIV-MFVUMRCOSA-N |
Bremelanotide is a synonym for PT-141. It is not a second sequence. PT-14 is an older development code for the same chain.
Reading the sequence
Four residues carry the pharmacology: His, D-Phe, Arg, Trp. That His-Phe-Arg-Trp motif runs through every melanocortin ligand, endogenous or synthetic. The D-configuration at phenylalanine blocks the proteolysis that clears the native hormone.
Norleucine at the N-terminus replaces methionine. That swap removes a sulphur that would oxidise. The N-terminal acetyl closes that amine. The C-terminus is a free carboxylic acid. That acid is the whole difference from melanotan II.
The lactam bridge
An amide links the Asp side chain to the Lys side chain, closing a 23-membered ring. Cyclisation fixes the pharmacophore in the bound conformation rather than leaving it to find that shape by chance.
A linear impurity with an unformed ring shares the elemental composition of the hydrolysed product. Ring closure needs chromatographic confirmation. Mass alone will not finish that check.
PT-141 is melanotan II minus one nitrogen
The relationship is exact and worth stating in atoms. Melanotan II carries the formula C50H69N15O9. PT-141 carries C50H68N14O10. One NH becomes one O.
That single swap converts the C-terminal amide into a free carboxylic acid. Nothing else moves. Both compounds share the InChIKey stereochemical block MFVUMRCOSA, so every stereocentre matches.
Why the lineage matters as structure
Dorr and colleagues put the amide parent, melanotan II, into the early literature [3]. Reviews then treat melanotan I, melanotan II and PT-141 as one structural lineage of melanocortin receptor agonists [4]. The useful fact is the atom count, not a product story.
Melanotan II is the amide. PT-141 is the acid. Melanotan I is a different, linear chain. Keep the three labels on three vials.
The tell for anyone assaying it
Mass spectrometry separates the pair by one unit, and the direction runs opposite to intuition. PT-141 is heavier at 1025.2 against 1024.2, because the substitution trades NH for the heavier O. A supplier confusing the two ships a compound one dalton light, not one dalton heavy.
Write both formulas on the certificate line. A name without a mass is how those two literatures contaminate each other.
PT-141 against the rest of the melanocortin family
Five ligands cover most of the published work, and their identity data separate them cleanly.
| Compound | Core | Formula | MW | Design |
|---|---|---|---|---|
| alpha-MSH | Linear tridecapeptide | C77H109N21O19S | 1664.9 | Endogenous ligand |
| Melanotan I | Linear tridecapeptide | C78H111N21O19 | 1646.8 | Full-chain analogue |
| Melanotan II | Cyclic heptapeptide amide | C50H69N15O9 | 1024.2 | Lactam, C-terminal amide |
| PT-141 | Cyclic heptapeptide acid | C50H68N14O10 | 1025.2 | Lactam, C-terminal acid |
| Setmelanotide | Cyclic octapeptide | C49H68N18O9S2 | 1117.3 | Disulfide, MC4R-selective |
Two different design strategies
Melanotan I keeps the full 13-residue chain and substitutes two positions. PT-141 throws the chain away and keeps only the pharmacophore, held in a ring. Both approaches beat the native hormone on stability. They arrive there by opposite routes.
Setmelanotide shows the third route. It reaches genuine MC4R selectivity through a disulfide-closed octapeptide [19]. That is why later metabolic work used that scaffold rather than this acid.
What this means for a comparison experiment
Any panel comparing these compounds needs matched conditions. The cyclic pair sits near 1025 daltons and the linear pair near 1650, so a single chromatographic method rarely resolves all four well. Calcium dependence adds a second variable [6].
Yuan and Tao map the ligand class beyond the native hormones [5]. Use that review for receptor subtype language. Do not use it as a use document.
The receptor and where PT-141 binds
Five melanocortin receptors exist. MC1R governs pigmentation chemistry. MC2R responds to adrenocorticotropin. MC3R with MC4R sit mainly in the central nervous system [5]. PT-141 activates several subtypes rather than one.
A solved structure
The 2021 cryo-EM work resolved four MC4R complexes: with the endogenous ligand alpha-MSH, with afamelanotide, with a small-molecule agonist, and with bremelanotide [1]. Peptide agonists share a conserved binding mode. Small molecules do not. That is why subtype selectivity has been so hard to engineer on the peptide side.
A companion structure of MC4R with setmelanotide added a mechanistic detail with practical consequences. Calcium is necessary for agonist efficacy but not for antagonist binding (PMID 33858992) [6]. Assay buffers therefore change the answer.
Selectivity is a matter of degree
Reviews of melanocortin pharmacology describe the whole ligand class as poorly selective, with the shared pharmacophore as the reason [5]. MC4R is treated as the subtype most relevant to the observed effects in the papers that name it [7], not as the only receptor engaged.
Medicinal chemistry continues to attack this. A 2026 series of 14 mid-size macrocycles, built on melanotan II and related scaffolds, produced two selective MC4R antagonists and one selective agonist (PMID 42340853) [8]. Selectivity is achievable. The older peptides do not have it.
Pfaus and colleagues wrote the leading circuit account for this agonist [7]. That account is a hypothesis about preoptic dopamine. The hamster study below is the test that failed to reproduce the downstream reward signal [2].
What the 2025 hamster study did not find
A female Syrian hamster study set out to locate the mechanism in the mesolimbic dopamine system [2]. Its results run against the expected account. That is why it deserves reading in full rather than in summary.
Where the receptors sit
Most MC3R and MC4R mRNA appeared in dopamine neurons of the ventral tegmental area. In the nucleus accumbens and dorsal striatum, fewer neurons carried MC4R, and those rarely overlapped with D1 or D2 receptor neurons. Accumbens MC4R sat in interneurons instead.
The two negative results
Neither the low nor the high dose changed melanocortin receptor mRNA expression anywhere in that system. Sexual experience produced a conditioned place preference in these animals, and the peptide failed to enhance it.
The proposed mechanism holds that the compound acts on presynaptic MC4R in the medial preoptic area, raising dopamine release [7]. The hamster data do not contradict that anatomy. They fail to reproduce the downstream reward signal in the model tested. The authors present the result as discrepant.
Why a negative result carries weight here
Two features make this study hard to set aside. It looked in the right place, finding MC3R and MC4R message concentrated in ventral tegmental dopamine neurons exactly as the model predicts. And it tested two dose levels rather than one, so a simple exposure explanation does not cover the outcome.
The anatomical finding also complicates the account in its own right. Accumbens MC4R sat on interneurons and rarely on D1 or D2 neurons, so any dopaminergic effect in that region runs through an extra synapse. A mechanism written as direct action on reward neurons does not match the expression map.
Read together with the receptor structure [1], the picture is a compound whose molecular target is certain and whose behavioural pathway is inferred. Reference agonists are useful in precisely that state, because the open question is answerable with the reagent in hand.
Cell work and the metabolic receptor story
Two lines of work use the same receptor engagement for unrelated endpoints. One is in vitro. The other is a receptor-class review. Neither is a use protocol.
Glioblastoma cell lines
A 2024 study applied bremelanotide to human glioblastoma cell lines (PMID 39197897) [20]. It reduced survivin expression and induced cell death at concentrations that spared normal human cells. An MC3R and MC4R antagonist abolished both effects. Forced survivin overexpression prevented the cell death.
This is in vitro work in cell lines. It identifies the receptors as candidate targets. It says nothing about any intact organism. Antagonist rescue is the part that converts attribution into evidence.
The central melanocortin system as a metabolic map
MC4R agonism appears in satiety circuitry. Sweeney and colleagues review that map [19]. Setmelanotide, not this acid, is the selective tool in that space. Indexed metabolic papers on PT-141 exist [18]. Those human endpoints sit outside this profile.
Use [19] for receptor geography. Use [18] as a pointer. Do not lift body-weight figures from either into a laboratory notebook as a recipe.
Indexed papers sit outside this profile
A registration programme and several indexed clinical papers exist. Those human endpoints sit outside the scope of this profile. The list remains so a reader can find the papers.
What those papers are
Clayton, Kingsberg and Simon reported the large programme papers. Dhillon, Mayer and Cipriani mapped the name in reviews [13][14] and [15]. White and Clayton reported cardiovascular and safety files [16][17]. Spana reported a metabolic file [18].
Use those papers for chronology and synonyms. Do not use them as a use document. This profile will not quote desire scores, sexual-event counts, nausea rates, or an approval label as a product story.
What a laboratory still needs from that file
The file tells you the peptide reached large programmes. It does not identify an unknown vial. Intact mass at 1025.2 still does that work. A brand name on a slide is not a certificate.
MC4R chemistry also appears in those cardiovascular papers [16][17]. Receptor-driven pressure biology is a class topic. The millimetre-of-mercury plots stay on the PubMed page.
Calcium, buffers and assay design
Agonist efficacy at MC4R depends on calcium [6]. Antagonist binding does not. A binding number produced without that control is not comparable to one produced with it.
What to write in the methods
Write the calcium concentration. Name the receptor species. Say whether the assay is binding or function. Peptide agonists share a pose in the cryo-EM set [1]. Small molecules do not. Do not mix those two data types in one table without a note.
A panel that includes PT-141 and setmelanotide is a selectivity experiment only if both run in the same buffer [6][8]. A panel that includes melanotan II is a C-terminus experiment only if intact mass confirms which amide or acid went in [3][4].
What not to import from the human file
Do not import questionnaire endpoints into a cell assay [10]. Do not import completion rates into a hamster design [11]. Those numbers answer different questions. They do not calibrate a vial.
How to read a PT-141 study
Four questions separate a usable paper from a misleading one.
Which melanocortin peptide?
Melanotan I, melanotan II and PT-141 appear in overlapping literature and share a pharmacophore. Check the formula rather than the name. Reviews covering all three exist precisely because the field conflates them [4].
Which receptor subtype?
A paper reporting an MC4R effect in a system expressing several subtypes has attributed rather than isolated. Antagonist controls, as in the glioblastoma work [20], are what convert attribution into evidence.
Which model?
Cell line, hamster, and a large indexed programme answer different questions. The hamster result [2] and the programme papers [10] are both sound and do not settle each other.
Was calcium controlled?
Agonist efficacy at MC4R depends on it [6]. A binding number produced without that control is not comparable to one produced with it.
Verifying research material
PT-141 is a defined chemical entity with published identifiers, so verification is arithmetic rather than judgement. Batch documentation sits on the certificates of analysis page.
Identity
Formula C50H68N14O10 and InChIKey FFHBJDQSGDNCIV-MFVUMRCOSA-N. Mass spectrometry should return a molecular weight near 1025.2, and the doubly charged ion is the practical precursor. A result near 1024.2 indicates melanotan II.
| Check | What it answers | What it cannot see |
|---|---|---|
| Intact mass 1025.2 | Acid versus amide parent | D-Phe versus L-Phe |
| Doubly charged precursor | Practical MS ion | Ring-open linear impurity if mass matches hydrolysis |
| Peptide map | Sequence coverage | Lactam closure without a chromatographic trace |
| Chiral amino acid analysis | D-Phe at position 7 | A second impurity that is not an amino acid |
| Calcium in the functional assay | Agonist efficacy at MC4R [6] | Identity of the solid |
Purity and stereochemistry
The D-phenylalanine at position 7 defines the molecule, and mass spectrometry cannot see it. An epimer carries the same formula and the same mass. Chiral amino acid analysis after hydrolysis answers the question. Nothing cheaper does.
The lactam bridge needs its own check. A linear impurity with an unformed ring shares the elemental composition of the hydrolysed product, so ring closure needs chromatographic confirmation rather than mass alone.
Handling
Tryptophan and histidine both absorb ultraviolet light and degrade under it. Suppliers ship the material lyophilised for that reason. A reconstituted unformulated peptide carries none of the stabilisation a finished product provides.
Two degradation routes matter for assay work. Tryptophan oxidises, which shifts mass by 16 daltons and shows up as a late-eluting shoulder. The lactam bridge hydrolyses under acid, opening the ring and adding 18 daltons. Both products retain enough of the parent signal to pass a careless identity check.
Store lyophilised material cold and dark, and treat aliquot count as a real variable. Freeze-thaw cycling degrades cyclic peptides faster than the storage interval alone predicts, so a vial opened weekly and a vial opened once are not equivalent starting material even at the same nominal age.
Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.
The rest of the melanocortin family sits in the peptides category.
Common questions about PT-141
Is PT-141 the same thing as bremelanotide? Yes. One compound, two names, plus the development code PT-14.
How does it differ from melanotan II? By one atom. The C-terminal amide becomes a carboxylic acid, taking the formula from C50H69N15O9 to C50H68N14O10 [3][4].
Is it selective for MC4R? No. It activates several melanocortin subtypes, and MC4R is treated as the most relevant one in the papers that name it [7]. Genuinely selective macrocycles came later [8].
What is the strongest evidence for a mechanism? The receptor structure [1]. The behavioural mechanism has weaker support and one recent negative result [2].
Why does calcium appear in binding protocols? Agonist efficacy at MC4R requires it, while antagonist binding does not, so buffer composition changes the measured potency [6].
Which melanocortin peptide is actually MC4R-selective? Setmelanotide, a disulfide-closed octapeptide, rather than any compound in the melanotan lineage [19]. Selective macrocycles reported in 2026 came from a separate design effort [8].
Does this page report human outcomes? No. Indexed clinical papers are listed so they can be found. This profile stops at chemistry, receptor structure and animal systems.
Summary of the evidence
Write the name, the mass and the receptor on the first line of a notebook page. Everything else in this profile is a check on those three facts.
Identity and what remains open
Identity: cyclic heptapeptide acid, C50H68N14O10, 1025.2 Da, CAS 189691-06-3, InChIKey FFHBJDQSGDNCIV-MFVUMRCOSA-N. PubChem CID 9941379 closes the record. A certificate that omits intact mass and D-Phe is not finished.
PT-141 is the long name for that lot. Bremelanotide and PT-14 are the same chain. Do not treat a synonym as a second compound.
If a methods section names PT-141 and then quotes 1024.2, stop. That mass belongs to melanotan II. The rest of that paper is about a different reagent. The same rule applies in reverse. This is the cheapest way to keep two melanocortin literatures from contaminating each other, and it costs one intact-mass line. Keep the certificate next to the notebook.
Design: a lactam-closed His-D-Phe-Arg-Trp pharmacophore with a C-terminal acid [3][4]. The amide parent is melanotan II. The selective later tool is setmelanotide [19].
Receptor evidence: a solved cryo-EM pose in MC4R [1], calcium-dependent agonist efficacy [6], and poor subtype selectivity across the older peptides [5][7]. Newer macrocycles show selectivity is possible [8].
Animal and cell evidence: a 2025 hamster study that did not move receptor mRNA or enhance conditioned place preference [2], and an in vitro glioblastoma series that needed an MC3R/MC4R antagonist to cancel the effect [20].
Limits: human desire scores, event counts, nausea rates and approval labels are out of scope here. Those papers remain in the reference list [9][12].
Status: supplied for laboratory research use only.
References
- Zhang H, Chen LN, Yang D, Mao C, Shen Q, Feng W, Shen DD, Dai A, et al. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell Res. 2021;31(11):1163-1175. PMID 34433901. DOI
- Borland JM, Kohut-Jackson AL, Peyla AC, Hall MA, Mermelstein PG, Meisel RL. Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder. Neuropharmacology. 2025;267:110299. PMID 39793696. DOI
- Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-1784. PMID 8637402. DOI
- Uckert S, Bannowsky A, Albrecht K, Kuczyk MA. Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies. Expert Opin Investig Drugs. 2014;23(11):1477-1483. PMID 25096243. DOI
- Yuan XC, Tao YX. Ligands for melanocortin receptors: beyond melanocyte-stimulating hormones and adrenocorticotropin. Biomolecules. 2022;12(10):1407. PMID 36291616. DOI
- Israeli H, Degtjarik O, Fierro F, Chunilal V, Gill AK, Roth NJ, Botta J, Prabahar V, et al. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. Science. 2021;372(6544):808-814. PMID 33858992. DOI
- Pfaus JG, Sadiq A, Spana C, Clayton AH. The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women. CNS Spectr. 2022;27(3):281-289. PMID 33455598. DOI
- Merlino F, Jia L, Boccino I, Carotenuto A, Tammaro F, Santoro F, Thompson PE, Grieco P. Goldilocks-inspired design of mid-size macrocycles for selective targeting of human melanocortin receptors. J Med Chem. 2026;69(15):18800-18812. PMID 42340853. DOI
- Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond). 2016;12(3):325-337. PMID 27181790. DOI
- Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials. Obstet Gynecol. 2019;134(5):899-908. PMID 31599840. DOI
- Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH. Long-term safety and efficacy of bremelanotide for hypoactive sexual desire disorder. Obstet Gynecol. 2019;134(5):909-917. PMID 31599847. DOI
- Simon JA, Kingsberg SA, Portman D, Jordan R, Lucas J, Sadiq A, Krop J, Clayton AH. Prespecified and integrated subgroup analyses from the RECONNECT phase 3 studies of bremelanotide. J Womens Health (Larchmt). 2022;31(3):391-400. PMID 35230162. DOI
- Dhillon S, Keam SJ. Bremelanotide: first approval. Drugs. 2019;79(14):1599-1606. PMID 31429064. DOI
- Mayer D, Lynch SE. Bremelanotide: new drug approved for treating hypoactive sexual desire disorder. Ann Pharmacother. 2020;54(7):684-690. PMID 31893927. DOI
- Cipriani S, Alfaroli C, Maseroli E, Vignozzi L. An evaluation of bremelanotide injection for the treatment of hypoactive sexual desire disorder. Expert Opin Pharmacother. 2023;24(1):15-21. PMID 36242769. DOI
- White WB, Myers MG, Jordan R, Lucas J. Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide. J Hypertens. 2017;35(4):761-768. PMID 27977473. DOI
- Clayton AH, Kingsberg SA, Portman D, Sadiq A, Krop J, Jordan R, Lucas J, Simon JA. Safety profile of bremelanotide across the clinical development program. J Womens Health (Larchmt). 2022;31(2):171-182. PMID 35147466. DOI
- Spana C, Jordan R, Fischkoff S. Effect of bremelanotide on body weight of obese women: data from two phase 1 randomized controlled trials. Diabetes Obes Metab. 2022;24(6):1084-1093. PMID 35170192. DOI
- Sweeney P, Gimenez LE, Hernandez CC, Cone RD. Targeting the central melanocortin system for the treatment of metabolic disorders. Nat Rev Endocrinol. 2023;19(9):507-519. PMID 37365323. DOI
- 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 Res. 2024;44(9):3875-3883. PMID 39197897. DOI
PT-141 (Bremelanotide) is sold for laboratory research use only. Not for human consumption, nor medical, veterinary, or household uses.
