PT-141 complete guide

PT-141 (bremelanotide) is a cyclic 7-amino-acid alpha-MSH analog derived from the Melanotan-2 (MT-2) cyclic-melanocortin lineage that originated in the Hruby laboratory at the University of Arizona in the 1980s. Subsequent medicinal-chemistry work at Palatin Technologies and partners modified the parent cyclic peptide — principally by replacing the C-terminal amide of MT-2 with a free carboxyl group — to produce a compound with a shifted melanocortin-receptor selectivity profile, biased away from MC1R (and the broader pigmentary biology) and toward MC4R, the central melanocortin receptor most heavily implicated in appetite regulation and sexual-function neural circuits. The result is structurally adjacent to MT-2 but pharmacologically distinct: same macrocycle backbone, same Nle and D-Phe substitutions, single C-terminal modification, materially different research-application profile.

This positions PT-141 as the most-studied MC4R-focused melanocortin agonist with a full clinical-translational pathway. The research literature spans early phase-I work on penile-erection and subjective sexual response in research-animal-model and clinical-translational designs through to the RECONNECT phase-3 trials and the 2019 FDA approval of bremelanotide as Vyleesi for hypoactive sexual desire disorder (HSDD) in premenopausal women. This makes PT-141 unusual in the melanocortin family — it is one of the few peptides in this class to have crossed from research probe to fully FDA-approved prescription medicine. The clinical-translational pathway is interesting research context. The research-grade material we supply is for laboratory research only, and is not a substitute for prescription Vyleesi in any sense. This guide documents what the published peer-reviewed research has investigated, in mechanism-focused, research-frame language only.

Quick reference — PT-141 identifiers

Property	PT-141 (bremelanotide)
Class	Cyclic 7-amino-acid MC4R-focused melanocortin agonist; cyclic alpha-MSH analog
Sequence	Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH — 7 amino acids, lactam-cyclized; differs from MT-2 in the free carboxyl C-terminus (MT-2 carries an amide)
Other names	Bremelanotide, Vyleesi, PT-141
Molecular formula	C50H68N14O10
Molecular weight	1025.18 g/mol
CAS	189691-06-3
Origin	Palatin Technologies and partners; derivative of the MT-2 / Hruby lab cyclic-melanocortin lineage, with C-terminal amide→carboxyl modification shifting MC-subtype selectivity
Regulatory status	FDA-approved in 2019 as bremelanotide / Vyleesi for HSDD in premenopausal women. Research-grade material at TogoPeptide is supplied for laboratory research only and is not a substitute for prescription Vyleesi.
Receptor activity	Agonist at MC3R, MC4R and (to a lesser extent) MC5R; reduced MC1R activity relative to MT-2; MC2R (the ACTH receptor) is unaffected
Vial strengths (TogoPeptide)	10 mg lyophilized — for laboratory research only

Origin and structure — MC4R-selective derivative

To understand PT-141 it helps to first understand MT-2. Melanotan-2 was developed in the Hruby laboratory at the University of Arizona during the 1980s structure–activity programme on melanocortin-receptor agonists. Truncating native alpha-MSH to seven residues, replacing methionine with norleucine to resist oxidation, swapping in D-phenylalanine at position 7, and cyclizing via a lactam bridge between Asp(5) and Lys(10) produced a cyclic peptide with broad-spectrum agonism across MC1R, MC3R, MC4R and MC5R. MT-2's broad-spectrum profile is a research feature — it makes the compound a versatile probe across multiple melanocortin axes — and a complication, since in-vivo outcomes can be driven by signaling at multiple MC subtypes simultaneously.

Subsequent medicinal-chemistry work at Palatin Technologies set out to produce a cyclic alpha-MSH analog with a tighter receptor profile, better suited to research and clinical translation in indications driven by central rather than pigmentary melanocortin biology. The resulting compound — PT-141, later named bremelanotide — differs from MT-2 by a single, structurally subtle modification: the C-terminal amide of MT-2 is replaced by a free carboxyl group. The macrocycle, the Nle and D-Phe substitutions, and the seven-residue active core are otherwise preserved. That single change is enough to produce a compound with materially reduced MC1R affinity (less melanin-synthesis effect) and proportionally greater MC4R-driven activity in published receptor-binding research. It is a textbook example of elegant medicinal chemistry: same cyclic-peptide core, single subtle modification, distinct receptor selectivity.

This selectivity shift is the reason PT-141 occupies a different position in the melanocortin family from its parent. MT-2 is research-only and broad-spectrum, with the melanin-synthesis line as the most-studied published direction. PT-141 is MC4R-focused, with the sexual-function and HPG-axis lines as the most-studied directions — and is the only compound in the immediate family with a fully FDA-approved clinical indication.

Mechanism — MC4R-focused agonism

PT-141's published research footprint is shaped by the MC4R-focused selectivity profile. Each receptor in the melanocortin family has its own tissue distribution and downstream biology; the shift away from MC1R and toward MC4R changes which axes drive the dominant published research outcomes.

MC4R activation — sexual function research

MC4R is best known as the central appetite-regulator in the melanocortin family — loss-of-function mutations in MC4R are the most common known cause of monogenic obesity in humans. Published research also documents MC4R-mediated effects on sexual-function neural circuits, including the medial preoptic area and surrounding hypothalamic regions implicated in central control of sexual response. PT-141 published research-animal-model and clinical-translational literature documents MC4R-mediated effects on these circuits, with downstream measurable changes in penile-erection research and in subjective sexual-response endpoints in clinical-translational designs [2]. This MC4R-and-sexual-function axis is the mechanistic basis for the bremelanotide / Vyleesi clinical-translational pathway in HSDD.

HPG-axis modulation

Published research also documents PT-141 effects on the hypothalamic-pituitary-gonadal (HPG) axis, including elevations in luteinizing hormone (LH) and downstream testosterone in research-animal designs. The mechanism appears to be indirect — MC4R-driven activation of upstream KISS1 / GnRH circuitry rather than direct gonadotrope action — consistent with the broader role of central melanocortin signaling in reproductive-axis regulation. This research line frames PT-141 as a probe of central-melanocortin / HPG-axis crosstalk in addition to the more familiar sexual-function-circuit research.

MC1R / MC3R / MC5R reduced activity

Compared to MT-2, PT-141 has reduced MC1R affinity — which translates to materially less melanin-synthesis effect in published research-animal models. MC3R and MC5R activation are also lower in the receptor-binding profile relative to MT-2's broad-spectrum signature. The selectivity shift away from MC1R and toward MC4R is precisely what underlies PT-141's different research-application profile: where MT-2 is dominantly used as a melanin-and-pigmentary probe, PT-141 is dominantly used as a sexual-function and central-melanocortin probe.

Appetite-modulation research

Like MT-2, PT-141 retains MC4R-mediated appetite-suppression effects in research-animal models — an unsurprising consequence of MC4R activation given the receptor’s central role in energy-balance circuitry. The appetite-research line is smaller than the sexual-function line in the published PT-141 literature, but it remains a documented secondary research direction and is mechanistically continuous with the broader MC4R-and-appetite literature framed by Cone’s Anatomy and regulation of the central melanocortin system review [5].

Sexual-function research literature

The sexual-function line is the most-studied published PT-141 research direction. Early phase-I research-animal-model and clinical-translational work documented MC4R-mediated effects on penile-erection neural circuits and on subjective sexual-response endpoints in research designs [2], with parallel published work on the broader melanocortinergic control of penile erection establishing MC4R as the core receptor mediating these effects [4]. Subsequent published research extended this line into early subjective-sexual-response work in premenopausal women with sexual arousal disorder, providing the mechanistic and translational scaffolding for later phase-3 development [1].

This translational research framing is what made PT-141 unusual in the melanocortin family. Most melanocortin research compounds remain confined to research-animal-model and exploratory clinical-translational work; PT-141 progressed through the full FDA-approval pathway and emerged on the other side as a prescription medicine with a defined indication.

HSDD clinical-translational pathway

The bremelanotide development programme run by Palatin Technologies and AMAG Pharmaceuticals culminated in the RECONNECT phase-3 trials — two parallel randomised placebo-controlled studies of bremelanotide for hypoactive sexual desire disorder (HSDD) in premenopausal women, published in Obstetrics & Gynecology in 2019 [3]. Based on these trials, the FDA approved bremelanotide under the brand name Vyleesi in June 2019, making it (alongside flibanserin) one of the very small number of drugs approved for HSDD — and one of an even smaller number of fully-approved peptide therapeutics in the broader melanocortin space.

This is interesting research context. It does not change the regulatory status of the research-grade material at TogoPeptide. The Vyleesi prescription product is a manufactured, dose-titrated pharmaceutical preparation supplied through prescriber oversight for a defined indication. The research-grade lyophilized PT-141 powder we supply is a different artefact, supplied for laboratory research only. Research-grade PT-141 is not Vyleesi and is not a substitute for prescription Vyleesi in any sense. If a defined HSDD indication is the question, prescription Vyleesi via a licensed prescriber is the answer. If laboratory melanocortin-receptor research is the question, research-grade PT-141 is supplied for that, and only for that.

Appetite + cardiovascular research

Beyond the dominant sexual-function and HPG-axis lines, smaller published PT-141 research lines document MC4R-mediated appetite modulation (continuous with the broader MC4R-and-energy-balance literature) and cardiovascular reflex effects — including the well-documented blood-pressure response to bremelanotide that featured in clinical-translational dosing-window research and informed the eventual labelling of Vyleesi. These secondary research lines round out the picture of PT-141 as a relatively MC4R-biased melanocortin probe with effects across multiple central-melanocortin-driven physiological axes.

PT-141 vs MT-2 vs MT-1 (afamelanotide)

Three structurally related melanocortin-research compounds with shared ancestry but different selectivities and different regulatory paths:

Compound	Structure	Receptor selectivity	Research / regulatory status
MT-1 (afamelanotide)	Linear 13-aa alpha-MSH analog	Broad MC, MC1R-anchored	FDA / EMA approved (Scenesse) for erythropoietic protoporphyria
MT-2	Cyclic 7-aa alpha-MSH analog (C-terminal amide)	Broad MC (MC1R–MC5R)	Research only — not approved in any jurisdiction
PT-141 (bremelanotide)	Cyclic 7-aa alpha-MSH analog (C-terminal carboxyl)	MC4R-focused; reduced MC1R	FDA approved (Vyleesi) for HSDD in premenopausal women. Research-grade material is not a substitute for prescription Vyleesi.

How to read the table: three structurally related cyclic and linear alpha-MSH analogs, three different MC-subtype profiles, three different regulatory positions. PT-141 occupies the MC4R-focused, FDA-approved position. MT-2 occupies the research-only broad-spectrum position. MT-1 occupies the linear, MC1R-anchored, FDA/EMA-approved-for-EPP position. Same parental hormone, three different points on the medicinal-chemistry / regulatory map.

Storage and handling

PT-141 ships as lyophilized powder. Standard research-handling practice documented in the published literature on cyclic melanocortin peptides:

• Lyophilized state: sealed at −20°C, protected from light. Stable for the manufacturer-stated window (typically 24+ months).
• Diluent: bacteriostatic water (0.9% benzyl alcohol) is the standard reconstitution diluent for cyclic peptides of this class.
• Reconstituted state: refrigerate at 2–8°C. Use within ~28 days under refrigeration.
• Avoid freeze-thaw cycles after reconstitution.

Each TogoPeptide PT-141 shipment includes a per-batch Certificate of Analysis with HPLC purity (target ≥98%), mass-spectrometry identity confirmation, lot number, manufacture date, analysis date. See how to read a COA or reconstitution methodology for the methodology details.

Cross-research lines and pairings

• KPV pairing context: KPV is the alpha-MSH C-terminal tripeptide (Lys-Pro-Val), derived from the same parent hormone as PT-141 but acting through an entirely different mechanism class — intracellular NF-κB modulation rather than melanocortin-receptor agonism. The two compounds share parental ancestry but research-application context, not mechanism. See the KPV complete guide for the full alpha-MSH-fragment mechanism walk-through.
• MT-2 comparison-research designs: direct receptor-selectivity comparisons between PT-141 and MT-2 are the cleanest way to isolate MC4R-driven from MC1R-driven effects in melanocortin research. See the Melanotan-2 complete guide for the parent-compound mechanism walk-through.
• Reconstitution math: documented in the reconstitution calculator for the 10 mg vial strength.

Closing

PT-141 (bremelanotide) is a cyclic 7-amino-acid alpha-MSH analog derived from the Melanotan-2 cyclic-melanocortin lineage with a single structural modification — C-terminal amide replaced by carboxyl — producing more selective agonism at MC4R, reduced MC1R-driven pigmentary effects, and a research-application profile dominated by sexual-function neural circuits, HPG-axis modulation, and central appetite regulation. Of the immediate cyclic-melanocortin family, PT-141 is the compound that crossed the full clinical-translational pathway and emerged in 2019 as the FDA-approved prescription medicine Vyleesi for HSDD in premenopausal women.

This guide documents what published peer-reviewed research has investigated. It is mechanism context for laboratory researchers, not therapeutic recommendation, not protocol guidance, and not a basis for self-administration of any kind. Research-grade PT-141 is supplied as lyophilized powder for laboratory research only. It is not Vyleesi, it is not a substitute for prescription Vyleesi, and it is not approved for human or veterinary use in research-grade form in any jurisdiction. If a defined HSDD indication is the question, prescription Vyleesi via a licensed prescriber is the appropriate route. The research-grade material we supply is for laboratory melanocortin-receptor research, and only for that.

Source PT-141 for laboratory research:

• PT-141 product page — full identifiers, 10 mg lyophilized vial, per-batch COA
• Essentials and other research compounds — full category listing
• Melanotan-2 complete guide — the parent cyclic alpha-MSH analog, broad-spectrum MC1R–MC5R agonism
• KPV complete guide — alpha-MSH C-terminal tripeptide, different mechanism class, same parent hormone

For methodology and laboratory-handling questions, contact our research-supply team at info@togopeptide.com.