FOR RESEARCH USE ONLY. NOT FOR HUMAN OR VETERINARY USE. NOT FOR HUMAN CONSUMPTION.
Compounds described on this site are supplied solely for laboratory research. They are not offered for human or veterinary use or for clinical use, and they are not intended to diagnose, mitigate, cure or prevent any disease.
PT-141, also identified as bremelanotide, is a synthetic cyclic heptapeptide and structural analogue of alpha-melanocyte-stimulating hormone, closed by a side-chain lactam between aspartate and lysine. Four publications are reviewed: a structural study of the peptide bound to the melanocortin-4 receptor, the design and safety record of two identical phase 3 trials, an ambulatory blood-pressure study and a programme-wide adverse-event review. The U.S. FDA has approved a drug product containing bremelanotide; the PepGenex research material is not that product, and the trial figures describe material prepared for those studies, not PepGenex lots.
At a glance
Also identified as
Bremelanotide
Class
Cyclic heptapeptide
Target or mechanism
Agonist — Melanocortin 4 receptor (MC4R)
Evidence types represented
in vitro, human
Published studies reviewed
4
Regulatory and registry records
1
Last reviewed
2026-09-24
U.S. FDA status
An FDA approved drug product containing bremelanotide (PT-141) exists. Source: Drugs@FDA, Application NDA 210557.
Overview
PT-141, also identified as bremelanotide, is a synthetic cyclic peptide of seven residues, and a structural analogue of alpha-melanocyte-stimulating hormone.
The publications on this page are of three kinds: a structural study that imaged bremelanotide bound to the melanocortin-4 receptor; the design of two identical randomised phase 3 trials; and the safety record — an ambulatory blood-pressure trial and a review of adverse events across the development programme.
Regulatory status
An FDA approved drug product containing bremelanotide (PT-141) exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
Imaged in a structural study bound to the melanocortin-4 receptor in its active, G-protein-coupled state, alongside the receptor's natural ligand. The publications recorded here do not characterise its activity at the other melanocortin receptors, and the human studies measured endpoints and safety, not mechanism.
Scope of the published work
Areas investigated
Receptor structural biology
Questionnaire endpoints
Blood pressure and heart rate
Tolerability
Models used
Receptor structures
Randomised human studies
Pooled safety review
Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.
Limitations
Evidence represented on this page: in vitro and human. No animal research is represented. The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Common questions
What is PT-141?
PT-141, also identified as bremelanotide, is a synthetic cyclic peptide of seven residues, and a structural analogue of alpha-melanocyte-stimulating hormone.
How does PT-141 work, according to the published research?
Imaged in a structural study bound to the melanocortin-4 receptor in its active, G-protein-coupled state, alongside the receptor's natural ligand. The publications recorded here do not characterise its activity at the other melanocortin receptors, and the human studies measured endpoints and safety, not mechanism.
Reports four high-resolution structures of the full-length melanocortin-4 receptor (MC4R) in complex with its heterotrimeric Gs protein, each with a different agonist bound: the natural peptide α-MSH, afamelanotide, bremelanotide, and the selective small molecule THIQ. (Zhang et al., 2021, PMID 34433901)
What has published research on PT-141 found, and what are its limits?
This page records 4 publications, reporting laboratory (in vitro) work in 1, human work in 3. Each is listed with its identifier under References.
Human studies represented: White et al., 2017, PMID 27977473; Clayton et al., 2022, PMID 35147466; Kingsberg et al., 2019, PMID 31599840.
Evidence represented on this page: in vitro and human.
No animal research is represented.
The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.
Is PT-141 approved by the U.S. FDA?
An FDA approved drug product containing bremelanotide (PT-141) exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
What risks have published studies of PT-141 reported?
3 published human studies on this page report adverse events or safety measurements. Each is listed with its publication in the adverse-events section of this page.
Trial events do not establish a complete safety profile.
What adverse events have been reported in published studies of PT-141?
Adverse events and safety measurements as reported by the published human studies on this page. Each entry is attributed to its publication.
White et al., 2017, PMID 27977473
Design and population
Randomised, double-blind, placebo-controlled, parallel-arm trial of bremelanotide in three active arms against placebo, in 397 premenopausal women with normal blood pressure or controlled hypertension. Ambulatory blood pressure and heart rate were recorded, with pharmacokinetic sampling alongside.
Events reported
In the 0-to-4-hour interval after each of two doses, ambulatory systolic blood pressure rose relative to placebo by 2.4 and 3.0 mmHg with the middle dose (P = 0.029 and 0.076) and by 3.1 and 3.2 mmHg with the highest dose (P = 0.006 and 0.027). Peak increases typically lasted less than 15 minutes, and similar increases were seen in diastolic pressure. The blood-pressure increases were accompanied by reductions in heart rate of 4.6 to 4.7 beats per minute in the 0-to-4-hour interval with the highest dose (P < 0.001). Twenty-six participants stopped after randomisation because of prespecified blood-pressure increases, in similar proportions across the four groups.
Clayton et al., 2022, PMID 35147466
Design and population
A review of the safety record of the whole clinical development programme: 3,500 participants in 43 completed studies, phases 1 to 3. In the phase 3 studies, participants used bremelanotide for up to 18 months.
Events reported
In the integrated double-blind portion of the phase 3 studies (N = 1,247), the most common adverse events with bremelanotide versus placebo were nausea (40.0% vs 1.3%), flushing (20.3% vs 1.3%), headache (11.3% vs 1.9%) and reactions where the dose was given (5.4% vs 0.5%). Nausea was the most common reason for stopping bremelanotide. There were no deaths; a few participants had serious adverse events. At the end of the double-blind portion of the phase 3 studies, 70% of the bremelanotide group went on to the open-label phase, against 87% of the placebo group. Focal hyperpigmentation was rare, but occurred in more than one-third of participants in a study of repeated consecutive use. Most drug–drug interactions studied were not clinically significant; the exceptions reported were lowered plasma concentrations of indomethacin and naltrexone.
Kingsberg et al., 2019, PMID 31599840
Design and population
Two identical phase 3, randomised, double-blind, placebo-controlled, multicentre trials (RECONNECT; studies 301 and 302), run between January 2015 and August 2016. Participants were randomised 1:1 to bremelanotide or to placebo, for 24 weeks. The coprimary endpoints were change from baseline to end of study in the FSFI desire-domain score and in item 13 of the Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO). 1,267 women were randomised; 1,247 formed the safety population and 1,202 the modified intent-to-treat population. Mean age was 39 years; 85.6% were white and 96.6% were enrolled at US sites.
Events reported
Nausea, flushing and headache were each reported more often with bremelanotide than with placebo, at 10% or more in both studies.
Trial events do not establish a complete safety profile.
Published research
Grouped by the kind of study. Select one to narrow what is shown below.
Laboratory (in vitro)(1)
Laboratory (in vitro)
Structural insights into ligand recognition and activation of the melanocortin-4 receptor.
Zhang H, Chen LN, Yang D, et al., Cell Research, 2021;31(11):1163-1175
published
Reports four high-resolution structures of the full-length melanocortin-4 receptor (MC4R) in complex with its heterotrimeric Gs protein, each with a different agonist bound: the natural peptide α-MSH, afamelanotide, bremelanotide, and the selective small molecule THIQ.
Together with pharmacological studies, reports that the peptide agonists — bremelanotide among them — share a conserved binding mode at MC4R, distinct from the way the small-molecule agonist is recognised.
Context
The structural study shows bremelanotide bound to one receptor, MC4R, in its active state. It does not establish that MC4R is the only receptor bremelanotide acts at, and nothing on this page measures its activity at the other four melanocortin receptors.
Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.
White WB, Myers MG, Jordan R, Lucas J., Journal of Hypertension, 2017;35(4):761-768
published
Randomised, double-blind, placebo-controlled, parallel-arm trial of bremelanotide in three active arms against placebo, in 397 premenopausal women with normal blood pressure or controlled hypertension. Ambulatory blood pressure and heart rate were recorded, with pharmacokinetic sampling alongside.
In the 0-to-4-hour interval after each of two doses, ambulatory systolic blood pressure rose relative to placebo by 2.4 and 3.0 mmHg with the middle dose (P = 0.029 and 0.076) and by 3.1 and 3.2 mmHg with the highest dose (P = 0.006 and 0.027). Peak increases typically lasted less than 15 minutes, and similar increases were seen in diastolic pressure.
The blood-pressure increases were accompanied by reductions in heart rate of 4.6 to 4.7 beats per minute in the 0-to-4-hour interval with the highest dose (P < 0.001). Twenty-six participants stopped after randomisation because of prespecified blood-pressure increases, in similar proportions across the four groups.
Human study (phase not stated)Human phase 3n = 3500
Safety Profile of Bremelanotide Across the Clinical Development Program.
Clayton AH, Kingsberg SA, Portman D, et al., Journal of Women's Health, 2022;31(2):171-182
published
A review of the safety record of the whole clinical development programme: 3,500 participants in 43 completed studies, phases 1 to 3. In the phase 3 studies, participants used bremelanotide for up to 18 months.
In the integrated double-blind portion of the phase 3 studies (N = 1,247), the most common adverse events with bremelanotide versus placebo were nausea (40.0% vs 1.3%), flushing (20.3% vs 1.3%), headache (11.3% vs 1.9%) and reactions where the dose was given (5.4% vs 0.5%). Nausea was the most common reason for stopping bremelanotide. There were no deaths; a few participants had serious adverse events.
At the end of the double-blind portion of the phase 3 studies, 70% of the bremelanotide group went on to the open-label phase, against 87% of the placebo group.
Focal hyperpigmentation was rare, but occurred in more than one-third of participants in a study of repeated consecutive use.
Most drug–drug interactions studied were not clinically significant; the exceptions reported were lowered plasma concentrations of indomethacin and naltrexone.
Limitations
In the phase 3 programme, nausea was reported by 40% of the bremelanotide group, and a smaller share of that group went on into the open-label phase than of the placebo group (70% against 87%). The ambulatory monitoring trial found small, short-lived rises in blood pressure after each dose — small in size, and measured in women whose blood pressure was normal or controlled.
Kingsberg et al., 2019 (title withheld on this site; see the publication record)
Kingsberg SA, Clayton AH, Portman D, et al., Obstetrics and Gynecology, 2019;134(5):899-908
published
Two identical phase 3, randomised, double-blind, placebo-controlled, multicentre trials (RECONNECT; studies 301 and 302), run between January 2015 and August 2016. Participants were randomised 1:1 to bremelanotide or to placebo, for 24 weeks. The coprimary endpoints were change from baseline to end of study in the FSFI desire-domain score and in item 13 of the Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO).
1,267 women were randomised; 1,247 formed the safety population and 1,202 the modified intent-to-treat population. Mean age was 39 years; 85.6% were white and 96.6% were enrolled at US sites.
Nausea, flushing and headache were each reported more often with bremelanotide than with placebo, at 10% or more in both studies.
Classification, structure, recorded targets, evidence types and FDA status only, each read from the two compounds' own pages. These comparisons do not compare study results.
Melanocortin-related peptides: PT-141 is a cyclic structural analogue of α-MSH; KPV is the α-MSH (11-13) tripeptide.
PT-141
KPV
Classification
Cyclic heptapeptide
Tripeptide, α-MSH (11-13)
Structure
Sequence Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys) (Asp–Lys side-chain lactam); formula C50H68N14O10
Sequence Lys-Pro-Val; formula C16H30N4O4
Targets recorded
Agonist: Melanocortin 4 receptor (MC4R)
PepT1 di/tripeptide transporter (uptake); NF-κB signalling (p65RelA nuclear import, in one cell line)
Evidence types represented
in vitro, human
in vitro, animal
Status with the U.S. FDA
An FDA approved drug product containing bremelanotide (PT-141) exists. Source: Drugs@FDA, Application NDA 210557.
Not shown (no Drugs@FDA application record verified for this page)
References
Published studies reviewed (4)
Structural insights into ligand recognition and activation of the melanocortin-4 receptor. — Zhang H, Chen LN, Yang D, et al., Cell Research, 2021;31(11):1163-1175
DOI 10.1038/s41422-021-00552-3 · PMID 34433901 · PMC8563965
Kingsberg et al., 2019 (title withheld on this site; see the publication record) — Kingsberg SA, Clayton AH, Portman D, et al., Obstetrics and Gynecology, 2019;134(5):899-908
DOI 10.1097/AOG.0000000000003500 · PMID 31599840 · PMC6819021 · NCT02333071
Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide. — White WB, Myers MG, Jordan R, Lucas J., Journal of Hypertension, 2017;35(4):761-768
DOI 10.1097/HJH.0000000000001221 · PMID 27977473 · PMC5338879
Safety Profile of Bremelanotide Across the Clinical Development Program. — Clayton AH, Kingsberg SA, Portman D, et al., Journal of Women's Health, 2022;31(2):171-182
