PT-141 10mg

Overview

PT-141 is the catalog designation for bremelanotide, a synthetic cyclic heptapeptide lactam described in the peer-reviewed literature as a non-selective agonist at the melanocortin receptor family.[1] Molinoff and colleagues published the original characterization of the compound as a melanocortin agonist in Annals of the New York Academy of Sciences.[1]

The molecule derives from the melanotropin structure-activity programme conducted at the University of Arizona, reviewed by Hadley and Dorr, which produced a series of superpotent α-MSH analogues including Melanotan II.[2] Bremelanotide is the deaminated derivative of that parent compound, carrying a C-terminal free acid where Melanotan II carries an amide — a single terminal change that alters the receptor-engagement profile while retaining the cyclic scaffold.[1][2]

Why the compound appears in the literature

Melanocortin receptors are a five-member family of class A G-protein-coupled receptors with distinct tissue distributions. Because bremelanotide engages several of these subtypes rather than one, it is used in receptor pharmacology as a non-selective tool ligand — typically alongside subtype-selective antagonists — to separate the contributions of individual melanocortin receptors in a given model system.[5][7] Van der Ploeg et al. established MC4R as the receptor subtype of interest for centrally mediated melanocortin pharmacology, and Cone and colleagues have reviewed the central melanocortin system in energy homeostasis.[3][6]

Regulatory status, reported factually

A pharmaceutical formulation of bremelanotide received U.S. FDA approval in 2019; Dhillon and Keam summarized that approval in Drugs.[13] That approval attaches to a specific manufactured pharmaceutical product under defined clinical conditions. The research-grade material supplied here is not that product, and nothing on this page describes or implies a clinical use for it.

A note on the published record

Investigators working with this compound should be aware that the bremelanotide clinical literature contains flagged records. One randomized trial of the compound was subsequently retracted, and a second study by the same author group carries a formal Expression of Concern issued by The Journal of Urology in 2023.[23] Separately, Spielmans published a re-analysis of the phase 3 programme contesting the magnitude of the reported effects.[22] Neither retracted nor Expression-of-Concern-flagged studies are cited as evidence anywhere on this page.

Research framework

Within the melanocortin research domain, PT-141 is most directly compared with Melanotan II for the amide-versus-free-acid terminal distinction and with KPV for the receptor-engagement versus PepT1-uptake distinction. The compound is supplied here strictly as a research reference standard for in vitro and animal-model investigation, and is not intended for human or veterinary use.

Reported Mechanism

1. Melanocortin Receptor Engagement

Bremelanotide is described as a non-selective agonist across the melanocortin receptor family — MC1R, MC3R, MC4R and MC5R — all members of the rhodopsin-like (class A) GPCR superfamily.[1][5] Reported potency is graded rather than subtype-selective, which is the property that makes the compound useful as a broad-spectrum reference ligand and, equally, the property that requires selective antagonists to be co-applied when a single subtype is under investigation.[5]

2. Structural Pharmacophore

The peptide retains the His-Phe-Arg-Trp core message sequence common to endogenous melanocortins, which is the determinant of receptor molecular recognition in this family.[2][5] Two engineered features distinguish it from the native hormone: a lactam bridge that constrains the backbone into the bioactive turn conformation, and a D-phenylalanine substitution that blocks proteolysis at the corresponding peptide bond.[2] Merlino et al. have since applied macrocycle design of this kind to engineer subtype selectivity across human melanocortin receptors.[20]

3. Receptor-Level Structural Biology

Zhang et al. reported cryo-EM structures resolving ligand recognition and activation at the melanocortin-4 receptor, defining the orthosteric pocket architecture and the conformational transitions that accompany agonist binding in this receptor family.[4] This structural work provides the framework for interpreting agonist behaviour at MC4R.

4. Downstream Signalling

Melanocortin receptor agonism couples principally through Gαs to adenylyl cyclase, elevating intracellular cAMP. Reported secondary events include calcium mobilization and β-arrestin recruitment with subsequent receptor internalization.[4][5]

5. Neuroanatomical Localization

Preclinical work localizes the compound's central activity using c-Fos immunoreactivity, a standard marker of neuronal activation. Systemic administration in animal models produces c-Fos labelling in the paraventricular nucleus and medial preoptic area of the hypothalamus, identifying these as sites of central engagement.[9][11] Giuliano reviewed the experimental basis for melanocortinergic signalling in the central nervous system.[7]

6. Receptor Cross-Reactivity Profile

Binding studies summarized in the melanocortin literature report no significant affinity at opioid, GABA, dopamine, serotonin or NMDA receptors, nor at the dopamine transporter — the compound's pharmacology is confined to the melanocortin family rather than extending across the classical neurotransmitter receptor panel.[10][12] MC2R, the ACTH receptor, is not engaged by melanocortin analogues of this class.[5]

Structural Comparison

Receptor-level and clinical findings summarized here were obtained with defined laboratory preparations or with the pharmaceutical formulation under controlled study conditions. No conclusions about research-grade material are implied.

Research Applications

Published investigations involving bremelanotide fall into the following areas of laboratory and clinical research. These describe the subject matter of the published record and are not statements of effect.

1. Melanocortin receptor pharmacology — Molinoff et al. published the original characterization of the compound as a melanocortin agonist, and Yuan and Tao reviewed the broader ligand landscape for these receptors.[1][5]
2. MC4R structural biology — Zhang et al. resolved ligand recognition and activation mechanisms at the melanocortin-4 receptor.[4]
3. Central melanocortin system research — Van der Ploeg et al. defined an MC4R role in centrally mediated melanocortin pharmacology; Sweeney, Cone and colleagues reviewed the central melanocortin system in metabolic regulation.[3][6]
4. Preclinical CNS neuroscience — Pfaus and colleagues published rodent studies and a review of central nervous system effects in animal models; Borland et al. reported analyses in a female Syrian hamster model.[8][9][19]
5. Melanocortin neurobiology reviews — Shadiack et al. and Pfaus et al. reviewed the melanocortin literature in this therapeutic area.[10][11][12]
6. Oncology cell-line research — Suzuki et al. reported that the compound induces cell death and growth inhibition in glioblastoma cells in vitro via suppression of survivin expression, an application entirely separate from the melanocortin neuroscience literature.[18]
7. Cardiovascular pharmacology — White et al. reported the use of ambulatory blood-pressure monitoring to assess this melanocortin receptor agonist.[14]
8. Analytical chemistry and peptide stability — Sauter et al. developed UHPLC-MS/MS quantification of the cyclic peptide; Yuvaraaj and Sharma characterized the acetate salt and its degradants by LC-HRMS/MS with computational modelling of epimerization.[15][16]
9. Forensic and supply-chain analysis — Mestria et al. applied LC-HRMS to characterize melanotan II and bremelanotide material obtained outside regulated supply chains, work directly relevant to material-identity verification.[17]
10. Receptor genetics — Bardhan et al. reviewed melanocortin receptor gene polymorphism and its association with inflammatory traits.[21]
11. Macrocycle design and subtype selectivity — Merlino et al. reported mid-size macrocycle design for selective targeting of human melanocortin receptors.[20]

Comparative Research Context

Within the melanocortin research literature, PT-141 is most directly compared with Melanotan II for the terminal amide-versus-free-acid distinction, and with KPV, an α-MSH fragment that enters cells through the PepT1 transporter rather than engaging melanocortin receptors at all.[2]

Research Summary

Foundational and Mechanistic Studies

Analytical and Material-Identity Studies

Mechanistic Themes

• Non-selective melanocortin agonism — engages multiple receptor subtypes rather than one, which is why selective antagonists are co-applied in subtype-resolution experiments
• Conformationally constrained scaffold — a lactam bridge and D-amino acid substitution stabilize the bioactive turn and resist proteolysis
• Gαs / cAMP coupling — with reported calcium mobilization and β-arrestin-dependent receptor internalization
• Central localization — c-Fos mapping identifies hypothalamic sites of engagement in animal models
• Pharmacologically confined — no significant reported affinity across the classical neurotransmitter receptor panel

Literature Integrity