PT-141 Research, Specifications & Scientific Information

Introduction

PT-141 is a cyclic heptapeptide built from the melanocortin message sequence — the His-Phe-Arg-Trp core that alpha-melanocyte-stimulating hormone, adrenocorticotropic hormone and every synthetic melanocortin share. What distinguishes it is not that core but the scaffolding around it: a lactam bridge closing a ring between positions 2 and 7, a D-phenylalanine in place of the L form, and an acetylated norleucine at the N-terminus. Those three modifications hold the recognition sequence in a fixed conformation and make the molecule stable enough to be a drug.

It became one. Developed by Palatin Technologies under the code PT-141 and the International Nonproprietary Name bremelanotide, it completed two identical phase 3 trials enrolling 1,267 participants ^[7] and a finished product containing it — VYLEESI, NDA 210557 — was approved by the U.S. Food and Drug Administration on 21 June 2019 for one specific indication in one specific population.

This page is about the peptide and its receptor pharmacology. The approval belongs to a finished pharmaceutical product, and the distance between those two things is the subject of the regulatory section below.

What Is PT-141?

PT-141 is a synthetic cyclic heptapeptide, Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH. It is a non-selective agonist at the melanocortin receptor family: five class A G protein-coupled receptors, MC1R through MC5R, that signal through Gs and cyclic AMP and sit in tissues as different as melanocytes, adrenal cortex and hypothalamus.

The FDA-approved label records the compound's order of potency across those subtypes as MC1R, MC4R, MC3R, MC5R, MC2R, and states that at therapeutic exposures binding at MC1R and MC4R is the most relevant. MC4R-expressing neurons are distributed widely through the central nervous system; MC1R is expressed on melanocytes, where activation drives melanin expression and increased pigmentation.

One sentence on that label deserves to be read carefully, because it is unusual and it is the regulator's own: the mechanism by which the product improves its approved indication is unknown. A characterised receptor pharmacology and an unknown clinical mechanism are entirely compatible, and this compound is the clearest example of that in the library.

The approval itself is narrow and specific. It covers VYLEESI (bremelanotide injection), a particular finished product, for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder. Its label carries two explicit limitations of use: the product is not indicated for that condition in postmenopausal women or in men, and it is not indicated to enhance sexual performance. None of it extends to research-grade material supplied for laboratory use, which is a different substance in a different form made to a different standard.

PT-141 Specifications

This sequence cannot be written in single-letter code. The molecule is a cyclic heptapeptide: an amide bridge — a lactam — joins the aspartate side chain at position 2 to the lysine side chain at position 7, closing a ring through the middle five residues. Position 1 is norleucine, a non-proteinogenic residue, and its alpha-amino group is acetylated; position 4 is D-phenylalanine rather than the L form; the C-terminus is a free acid. The ring, the D-residue and the N-terminal acetyl together lock the His-D-Phe-Arg-Trp core — the message sequence shared by the melanocortin peptides — into the conformation that the receptor recognises, and they make the molecule far more stable than the linear hormone it was derived from. Bremelanotide is the des-amino, ring-opened-at-the-C-terminus relative of melanotan II: the two differ at the C-terminal position, one carrying a free acid and the other a primary amide, and that single difference separates two compounds with quite different research histories. The identifiers here are the records held by PubChem (CID 9941379), which carries CAS registry number 189691-06-3 and FDA/NCATS UNII code 6Y24O4F92S. The approved pharmaceutical product contains the acetate salt: the FDA label records bremelanotide acetate as C50H68N14O10 · xCH3COOH with 1 ≤ x ≤ 2, and states the molecular weight 1025.2 as that of the free base. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does PT-141 Work?

At the receptor, the answer is well characterised. Beyond the receptor, it is not.

The melanocortin receptors are among the smallest class A G protein-coupled receptors and they share an agonist recognition motif, which is why selectivity between them has been difficult to engineer and why a molecule built on that motif activates all five. PT-141 retains the motif and does not discriminate: the label's potency ordering puts MC1R first and MC4R second, with the other three below them.

MC4R is the subtype of interest for central effects. It is the receptor through which the melanocortin system participates in the central regulation of food intake and body weight, and it is expressed on neurons throughout the central nervous system. In the medial preoptic area of the hypothalamus in particular, MC4R has been proposed as the site at which this compound acts, by way of presynaptic receptors whose activation increases dopamine release ^[10].

That proposal is a hypothesis drawn from rodent work, and it is presented as one in the source. The regulator's position is the more conservative of the two and is quoted above.

MC1R activity is the other half of the pharmacology and is often left out of accounts of this compound. It is the receptor on melanocytes, and its activation leads to melanin expression and increased pigmentation. Because the compound's potency at MC1R is recorded as higher than at MC4R, that is not a marginal off-target property — it is the primary receptor interaction by potency.

PT-141 Mechanism of Action

In vitro research

Receptor-level characterisation. The FDA-approved label's potency ordering across the five melanocortin receptor subtypes — MC1R, MC4R, MC3R, MC5R, MC2R — is the most authoritative statement available on this molecule's receptor profile, and it establishes the compound as non-selective rather than MC4R-targeted.

Structural biology. Four high-resolution structures of full-length MC4R in complex with heterotrimeric Gs were reported in 2021, bound respectively to the endogenous peptide alpha-MSH, to two approved drugs — afamelanotide and bremelanotide — and to the small-molecule agonist THIQ. The work resolved the conserved binding mode of the peptide agonists, the distinctive recognition of small molecules that underlies subtype selectivity, and an activation mechanism distinctive to MC4R ^[11].

Two things follow from that paper for this page. The first is that the binding mode of this peptide at MC4R is now known at near-atomic resolution — a level of mechanistic detail that few compounds in this library have. The second is the paper's own framing: it describes low agonist selectivity and the absence of structural information as having hampered the development of MC4R-selective agents, which places this compound firmly on the non-selective side of the field it helped define.

A note on where the molecule came from. The peptide is an analogue of alpha-melanocyte-stimulating hormone, described from the outset as a melanocortin agonist acting at central receptors ^[1]. Its structural relationship to the other synthetic melanocortins is a matter of terminal chemistry rather than of core sequence, and is set out in the chemistry section below.

Findings in this section were obtained in receptor and structural systems. Nothing in them establishes anything about intact animals or about humans.

What Is PT-141 Being Researched For?

• Hypoactive sexual desire disorder in premenopausal women — two identical phase 3 trials ^{[7, 14, 15]}, a 52-week open-label extension ^[8], a phase 2b responder analysis ^[6] and prespecified subgroup analyses ^[13].
• Cardiovascular safety of melanocortin receptor agonism — a dedicated randomised ambulatory blood pressure study ^[5] and a programme-wide safety review ^[12].
• Melanocortin receptor structural biology — cryo-electron microscopy of MC4R with this peptide among its bound ligands ^[11].
• Central nervous system melanocortin neurobiology — rodent behavioural pharmacology ^{[3, 4]} and its interpretation ^[10].
• Earlier clinical pharmacology — a randomised study in premenopausal women ^[2] following the compound's first description ^[1].

Each of those is research into a pharmaceutical product candidate, conducted by or for its sponsor. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on PT-141

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Ambulatory blood pressure, phase 2

Population. 397 premenopausal women with normotension or controlled hypertension, randomised in a double-blind placebo-controlled parallel-arm trial across three amounts of the compound: 0.75, 1.25 and 1.75 mg subcutaneously ^[5].

Endpoint. Ambulatory systolic and diastolic blood pressure and heart rate, with pharmacokinetic exposure measured alongside ^[5].

Result. Ambulatory systolic pressure rose relative to placebo by 2.4 and 3.0 mmHg in the zero-to-four-hour interval following administration; peak increases typically lasted less than 15 minutes, and similar increases were seen in diastolic pressure. The rises were accompanied by reductions in heart rate over the same interval at the 1.75 mg amount. Participants were withdrawn for pre-specified blood pressure increases in similar proportions across all four groups ^[5].

Why this study exists. Melanocortin receptor agonists binding MC4R can raise blood pressure, and the trial was designed to characterise that directly rather than to rely on clinic measurements. Its result shaped the monitoring built into the later trials. It is a good example of a development programme testing its own known mechanistic liability.

RECONNECT, two identical phase 3 trials

Population. 1,267 premenopausal women with hypoactive sexual desire disorder randomised 1:1 across two identical trials — study 301 and study 302 — with 1,247 in the safety analysis and 1,202 in the efficacy analysis. Participants were 85.6% White, 96.6% from United States sites, mean age 39 years ^{[7, 14, 15]}.

Endpoint and duration. 24 weeks of 1.75 mg administered subcutaneously as needed, against placebo. Co-primary endpoints: change from baseline to end of study in the Female Sexual Function Index desire domain score, and in item 13 of the Female Sexual Distress Scale-Desire/Arousal/Orgasm ^[7].

Result. Both co-primary endpoints reached statistical significance in both trials. Change in the desire domain score against placebo was 0.30 in study 301 (p < 0.001) and 0.42 in study 302 (p < 0.001), 0.35 across the integrated studies (p < 0.001). Change in the distress item against placebo was −0.37 in study 301 (p < 0.001) and −0.29 in study 302 (p = 0.005), −0.33 integrated (p < 0.001) ^[7].

Adverse events. Nausea, flushing and headache each in 10% or more of treated participants in both trials, at higher rates than placebo ^[7].

Limitations. The effect sizes are small in absolute terms on both questionnaire scales, and the difference between statistical significance and clinical meaningfulness on a patient-reported instrument is the substantive question these trials raise rather than settle. The populations were narrow — predominantly White, almost entirely United States — and the trials excluded the populations named in the label's limitations of use.

Open-label extension, 52 weeks

Population. Of 856 participants eligible after the 24-week double-blind core phase, 684 entered the 52-week open-label extension and 272 completed it ^[8].

Result. Treatment-emergent adverse events considered related to study drug were nausea in 40.4%, flushing in 20.6% and headache in 12.0%; nausea was the only severe such event experienced by more than one participant in both studies. Change from baseline to end of extension in the desire domain score ranged from 1.25 to 1.30 and in the distress item from −1.4 to −1.7 among participants who had received the compound in the core phase, against 0.70–0.77 and −0.9 among those who had received placebo. All statistical analyses were descriptive ^[8].

Limitations. 272 of 684 completing is a 40% completion rate, and at a 40% nausea rate the attrition and the tolerability profile are plainly related. Open-label, single-arm, descriptive statistics only: this extension characterises long-term safety, and it is not evidence of efficacy.

Programme-wide safety

The clinical development programme comprised 3,500 subjects across 43 completed studies, with phase 3 exposure of up to 18 months. The most common adverse events against placebo were nausea (40.0% vs 1.3%), flushing (20.3% vs 1.3%), headache (11.3% vs 1.9%) and injection-site reactions (5.4% vs 0.5%) ^[12].

Those placebo rates — around 1% — make the comparison unusually clean, and they establish that the tolerability profile belongs to the compound rather than to the setting.

Preclinical Research on PT-141

Animal research

The rodent work that preceded the clinical programme is worth describing because of how it was designed, and because the design was the point.

In female rats, the compound selectively stimulated solicitational behaviours. It did so without affecting lordosis, pacing or other sexual behaviours, without causing generalised motor activation, and without affecting the perception of sexual reward ^[3].

Three negative controls inside one experiment is what makes that result informative. A compound that increased every measured behaviour would be indistinguishable from a general stimulant; a compound that increased one class of behaviour while leaving reflexive measures, locomotion and reward perception unchanged is making a specific claim that can be checked. The authors note explicitly that a selective effect of this kind had not been reported previously, and that earlier work in this field had concentrated on reflexive components such as lordosis — an observation about the field's methods as much as about the compound.

A subsequent overview collected the preclinical central nervous system findings for the compound ^[4], and a later review placed them in a mechanistic frame: activation of presynaptic MC4R on neurons of the medial preoptic area of the hypothalamus, with increased dopamine release as the proposed consequence ^[10].

That mechanistic account is a hypothesis built on animal data, described as such in its source, and it has not been demonstrated in humans. The approved label's statement that the clinical mechanism is unknown stands against it, and the label is the more conservative and the more authoritative of the two.

Findings described in this section were observed in rats. Nothing in them establishes anything about humans.

Other Areas of PT-141 Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Two further strands of the clinical record deserve separate mention.

The phase 2b responder analysis. A phase 2b study across a range of administered amounts was reanalysed to ask not whether group means differed but how many individual participants crossed a defined threshold of change ^[6]. Responder analysis is a more demanding question than a mean difference, and on a patient-reported instrument it is the more informative one; it is also the analysis whose results shaped the amount carried into phase 3.

Prespecified and integrated subgroup analyses. The two RECONNECT trials were analysed together across prespecified subgroups ^[13]. Prespecified is the operative word: subgroup analyses planned before unblinding carry evidentiary weight that post hoc subgrouping does not, and the distinction is worth insisting on wherever a subgroup result is quoted.

Instrument development. A separate line of work addressed the measurement instruments themselves — whether questionnaire scales used as primary endpoints in this field are reliable and valid in the populations they are applied to ^[9]. Where an entire approval rests on change in a questionnaire score, the psychometric properties of that questionnaire are not a technicality; they are the evidence.

The earlier clinical work. A randomised study in premenopausal women reported an effect on subjective response measures ^[2], following the compound's initial description as a melanocortin agonist with a clinical rationale ^[1]. These are small early studies, and they are cited here for the history of the programme rather than for their results.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

PT-141 vs Related Compounds

Against melanotan II

One terminal group. Melanotan II is a cyclic heptapeptide carrying a C-terminal primary amide; bremelanotide carries a free carboxylic acid at that position and an acetylated N-terminal norleucine. The core ring and the message sequence are the same. Structural similarity of that degree is a reason to keep two compounds' evidence separate, not to merge it, and nothing established for one transfers to the other.

Against melanotan I

Melanotan I, afamelanotide, is a linear alpha-MSH analogue rather than a cyclic one, and it appears alongside bremelanotide as one of the four ligands in the published MC4R structures ^[11]. Both are approved compounds in different jurisdictions for different indications.

Receptor selectivity

PT-141 is non-selective across all five melanocortin subtypes, with MC1R first by potency on the approved label. Selective MC4R agonists have been pursued as a separate goal in the field precisely because non-selectivity is the norm for peptides built on this message sequence ^[11].

Against the ACTH-derived peptides

Semax is also derived from a melanocortin — adrenocorticotropic hormone — but it retains only the 4–7 fragment and lacks the arginine and tryptophan positions that carry most melanocortin receptor pharmacology. Shared ancestry, different pharmacology.

Regulatory position

A finished product containing this peptide is approved in the United States for one indication in one population, with two stated limitations of use. Approval is specific to a product, an indication and a jurisdiction, and it does not generalise to other melanocortin peptides or to laboratory reagents.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

PT-141 is a cyclic heptapeptide that cannot be written in single-letter code. PubChem carries the free base as compound identifier 9941379, with CAS registry number 189691-06-3 and FDA/NCATS UNII code 6Y24O4F92S, molecular formula C50H68N14O10 and molecular weight 1025.2.

The lactam ring. An amide bond between the aspartate side chain at position 2 and the lysine side chain at position 7 closes a ring through the intervening residues. That covalent constraint is what holds the His-D-Phe-Arg-Trp message sequence in the conformation the receptor recognises, and it is also the structural feature most likely to be incompletely formed in a poorly made batch: a linear, ring-open impurity has almost the same mass as the cyclic product — differing by the mass of water — and is a different molecule pharmacologically.

The D-phenylalanine at position 4. Substituting the D enantiomer at the phenylalanine of the message sequence is the classical modification that raises melanocortin potency and confers resistance to proteolysis. It is also invisible to mass spectrometry: the all-L impurity is an exact isomer, identical in mass, and distinguishing the two requires a chiral or chromatographic method rather than a mass check.

The acetylated norleucine at position 1. Norleucine is not a proteinogenic residue; it is the straight-chain isomer of leucine and replaces the oxidation-prone methionine of the natural hormone. The N-terminal acetyl blocks aminopeptidase attack. Together these remove the two commonest routes to degradation at the N-terminus.

Free acid, not amide. The C-terminus is a free carboxylic acid. This is the single point at which the molecule differs from melanotan II, and a supplier listing that names one compound while describing the other's terminal chemistry is describing neither correctly.

Salt form. The approved product contains the acetate, recorded on its label as C50H68N14O10 · xCH3COOH with 1 ≤ x ≤ 2 — a variable, not a fixed, stoichiometry. Peptide content by weight therefore varies with the salt, and a milligram figure is not a statement about the amount of peptide unless the salt form and its content are specified.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Molinoff PB, Shadiack AM, Earle D, et al.. PT-141: a melanocortin agonist for the treatment of sexual dysfunction Annals of the New York Academy of Sciences; 2003. PMID 12851303 doi:10.1111/j.1749-6632.2003.tb03167.x
2. Diamond LE, Earle DC, Heiman JR, et al.. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist The journal of sexual medicine; 2006. PMID 16839319 doi:10.1111/j.1743-6109.2006.00268.x
3. Pfaus JG, Shadiack A, Van Soest T, et al.. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist Proceedings of the National Academy of Sciences of the United States of America; 2004. PMID 15226502 doi:10.1073/pnas.0400491101
4. Pfaus J, Giuliano F, Gelez H. Bremelanotide: an overview of preclinical CNS effects on female sexual function The journal of sexual medicine; 2007. PMID 17958619 doi:10.1111/j.1743-6109.2007.00610.x
5. White WB, Myers MG, Jordan R, et al.. Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide Journal of hypertension; 2017. PMID 27977473 doi:10.1097/HJH.0000000000001221
6. Althof S, Derogatis LR, Greenberg S, et al.. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide The journal of sexual medicine; 2019. PMID 31277966 doi:10.1016/j.jsxm.2019.05.012
7. Kingsberg SA, Clayton AH, Portman D, et al.. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials Obstetrics and gynecology; 2019. PMID 31599840
8. Simon JA, Kingsberg SA, Portman D, et al.. Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder Obstetrics and gynecology; 2019. PMID 31599847 doi:10.1097/AOG.0000000000003514
9. Mayer D, Lynch SE. Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder The Annals of pharmacotherapy; 2020. PMID 31893927 doi:10.1177/1060028019899152
10. Pfaus JG, Sadiq A, Spana C, et al.. The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women CNS spectrums; 2022. PMID 33455598 doi:10.1017/S109285292100002X
11. Zhang H, Chen LN, Yang D, et al.. Structural insights into ligand recognition and activation of the melanocortin-4 receptor Cell research; 2021. PMID 34433901 doi:10.1038/s41422-021-00552-3
12. Clayton AH, Kingsberg SA, Portman D, et al.. Safety Profile of Bremelanotide Across the Clinical Development Program Journal of women's health (2002); 2022. PMID 35147466 doi:10.1089/jwh.2021.0191
13. Simon JA, Kingsberg SA, Portman D, et al.. Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide Journal of women's health (2002); 2022. PMID 35230162 doi:10.1089/jwh.2021.0225
14. 1. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder 2014. NCT02333071
15. 2. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder 2015. NCT02338960

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: PT-141 (Bremelanotide) specifications and lot documentation