Research Use Only. The information presented here is for scientific and educational purposes. These compounds are not intended for human consumption, self-administration, or therapeutic use.
Introduction
PT-141, cataloged in peptide research collections under the development designation bremelanotide, is a synthetic cyclic heptapeptide studied as an agonist of the melanocortin receptor system. It is structurally derived from alpha-melanocyte-stimulating hormone (alpha-MSH), one of the endogenous melanocortin peptides cleaved from the proopiomelanocortin (POMC) precursor. Laboratory interest in PT-141 centers on how a compact, conformationally constrained peptide engages the centrally expressed melanocortin subtypes MC3R and MC4R, and how that engagement is translated into intracellular signaling.
The sections below outline the reported molecular identity of PT-141, the wider melanocortin receptor family, and the second-messenger cascade that MC3R and MC4R activation is understood to drive in preclinical and in-vitro models. All material is presented for research use only, not for human consumption, and describes only what the compound has been investigated for in cell-based and animal studies, not any clinical or therapeutic outcome. For laboratories comparing melanocortin tools, PT-141 is frequently examined alongside related analogs such as Melanotan-2 and Melanotan-1.
What Is PT-141?
PT-141 is a cyclic heptapeptide, meaning seven amino acid residues arranged in a lactam-bridged ring that constrains the molecule into a stable, receptor-preferred conformation. It is closely related to the cyclic melanocortin agonist Melanotan-2 (MT-II) and is commonly described in the literature as its principal metabolite, differing at the C-terminus where a carboxyl group replaces the terminal amide. This ring structure is one reason melanocortin analogs of this type resist rapid enzymatic breakdown relative to the linear endogenous peptide.
Molecular identity
The values below reflect commonly reported laboratory attributes and are provided for comparison only.
| Attribute | Reported value |
|---|---|
| Peptide class | Cyclic heptapeptide, melanocortin receptor agonist |
| Research designation | PT-141 (bremelanotide) |
| Molecular formula | C50H68N14O10 |
| Approximate molecular weight | ~1025 g/mol |
| Sequence length | 7 residues (cyclic core) |
| Parent ligand | alpha-MSH analog |
The Melanocortin Receptor Family
The melanocortin system comprises five G-protein-coupled receptors, designated MC1R through MC5R, each with a distinct tissue distribution and set of studied associations. All five couple predominantly to the stimulatory G-protein (Gs) and, when activated, raise intracellular cyclic AMP. The endogenous agonists are the POMC-derived melanocortins (alpha-, beta-, and gamma-MSH and ACTH), while agouti and agouti-related peptide (AgRP) act as endogenous antagonists or inverse agonists at selected subtypes.
PT-141 is characterized in research as a non-selective agonist with measurable activity across several subtypes, but its central pharmacology is studied principally at MC3R and MC4R. The entries below reflect commonly reported laboratory attributes and are provided for comparison only.
| Receptor | Primary research localization | Studied associations |
|---|---|---|
| MC1R | Melanocytes, immune cells | Pigmentation signaling |
| MC2R | Adrenal cortex | ACTH response, steroidogenesis |
| MC3R | Central nervous system, periphery | Energy homeostasis, inflammatory modulation |
| MC4R | Hypothalamus and wider CNS | Feeding behavior, energy balance |
| MC5R | Exocrine glands | Secretory and sebaceous studies |
MC3R and MC4R Signaling
Receptor activation and cyclic AMP
When PT-141 occupies the orthosteric pocket of MC3R or MC4R, the resulting conformational shift is understood to activate the coupled Gs protein. The alpha subunit then stimulates adenylyl cyclase, catalyzing conversion of ATP into cyclic AMP (cAMP). Rising cAMP activates protein kinase A (PKA), which phosphorylates downstream targets including the transcription factor CREB. In receptor assays, this cascade is the standard readout used to quantify melanocortin agonist potency, typically measured as cAMP accumulation in cells expressing a single defined receptor subtype.
Central localization of MC3R and MC4R
Unlike MC1R, which is studied largely in peripheral pigment cells, MC3R and MC4R are densely represented in the central nervous system. MC4R in particular is concentrated in hypothalamic nuclei that research has linked to energy balance and feeding behavior, which is why MC4R signaling is a longstanding focus of neuroendocrine investigation. MC3R shows a complementary distribution and is examined in the context of energy partitioning and inflammatory signaling. Because PT-141 reaches these central receptors in animal models, it is used experimentally as a probe for mapping melanocortin circuitry.
Beyond the canonical pathway
Melanocortin receptors are also reported to recruit effectors beyond the Gs-cAMP axis, including mitogen-activated protein kinase (MAPK/ERK) cascades and, in some systems, beta-arrestin-dependent signaling. The balance between these arms, sometimes described as biased agonism, is an active area of receptor pharmacology and one reason cyclic analogs like PT-141 remain useful reference agonists for probing MC3R and MC4R behavior in vitro.
How PT-141 Is Studied in the Laboratory
Preclinical characterization of PT-141 typically combines radioligand or fluorescent binding assays, which estimate affinity for each cloned receptor, with functional cAMP assays that report agonist efficacy. Comparative studies frequently place PT-141 next to other melanocortin analogs to contrast selectivity profiles, ring chemistry, and stability. The figures below reflect commonly reported laboratory attributes and are provided for comparison only.
| Compound | Class | Approx. MW (g/mol) | Length | Receptor emphasis in research |
|---|---|---|---|---|
| PT-141 | Cyclic heptapeptide | ~1025 | 7 | MC3R and MC4R (also MC1R) |
| Melanotan-2 | Cyclic heptapeptide | ~1024 | 7 | Broad MC1R to MC5R |
| Melanotan-1 | Linear tridecapeptide | ~1647 | 13 | MC1R-preferring |
| alpha-MSH | Endogenous tridecapeptide | ~1665 | 13 | Endogenous pan-agonist |
Reproducible receptor work depends on well-characterized starting material, so laboratories reviewing melanocortin peptides commonly verify identity and purity against a certificate of analysis and third-party testing certificates before use. Documentation of this kind supports the reproducibility that receptor-level comparisons require. Related melanocortin research tools, including PT-141 itself, are cataloged in the broader research peptide collection.
Frequently Asked Questions
What is the mechanism of PT-141?
In research models, PT-141 acts as an agonist at melanocortin receptors, binding principally to MC3R and MC4R. Receptor activation stimulates the Gs protein and adenylyl cyclase, raising intracellular cyclic AMP and activating protein kinase A. This cAMP-driven cascade is the signaling event most often measured when the compound is characterized in vitro.
Which receptors does PT-141 target?
PT-141 is described as a non-selective melanocortin agonist with activity at MC1R, MC3R, and MC4R. Laboratory attention concentrates on the centrally expressed MC3R and MC4R subtypes because of their density in the central nervous system and their role in melanocortin circuit studies.
How is PT-141 different from Melanotan-2?
PT-141 and Melanotan-2 share the same cyclic heptapeptide core. They differ at the C-terminus, where PT-141 carries a carboxyl group in place of the terminal amide found in Melanotan-2. For this reason PT-141 is commonly described as the principal metabolite of Melanotan-2 in the research literature.
What does MC4R activation do in research studies?
MC4R is concentrated in hypothalamic regions that research associates with energy balance and feeding behavior. In preclinical work, MC4R activation is studied as a node in the neural circuitry that regulates these processes, which is why MC4R agonists are used as pharmacological probes.
Is PT-141 a peptide or a small molecule?
PT-141 is a peptide, specifically a cyclic heptapeptide of seven amino acid residues arranged in a lactam-bridged ring. Its constrained ring structure distinguishes it from linear melanocortin peptides and is associated with greater conformational stability in laboratory settings.
Is PT-141 available for any approved use?
Within this context PT-141 is handled strictly as a research chemical. It is offered for laboratory investigation only and is not intended for human consumption, self-administration, or therapeutic application. Its role here is limited to receptor-level and preclinical study.
References and Further Reading
- Cone RD and colleagues. Foundational work on the melanocortin-4 receptor and central energy homeostasis. PubMed: Cone melanocortin-4 receptor energy homeostasis
- Gantz I and colleagues. Molecular cloning and characterization of the melanocortin receptor subtypes. PubMed: Gantz molecular cloning melanocortin receptor
- Hruby VJ and colleagues. Design of conformationally constrained cyclic alpha-MSH analogs. PubMed: Hruby cyclic melanocortin analog
- Reviews of MC3R physiology and its role in energy partitioning and inflammatory signaling. PubMed: melanocortin-3 receptor physiology
- Bremelanotide (PT-141) as a melanocortin receptor agonist: preclinical pharmacology. PubMed: bremelanotide melanocortin receptor
- Melanocortin receptor signaling through Gs, adenylyl cyclase, and cyclic AMP. PubMed: melanocortin receptor cAMP signaling
- POMC-derived melanocortins and the regulation of central melanocortin circuits. PubMed: POMC melanocortin hypothalamus
