Stress-hormone fragment (Pro-opiomelanocortin [115-133])
A lab-made mouse peptide cut from POMC, the stress-hormone precursor, used in research to study how the body triggers cortisol release from the adrenal gland. Research tool only, not a medicine.
- Class
- Endogenous neuropeptide fragment (mouse POMC-derived)
- Status
- No approved therapeutic status identified
- Best-supported effect
- Used as a quantitation reference analyte in mouse pituitary peptidomics; no bioactivity claim is supported by the source
- Main caveat
- The compiled source contains no bioactivity, efficacy, or mechanistic evidence for this fragment
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Pro-opiomelanocortin [115-133] peptide is a 19-amino-acid fragment derived from POMC — a large precursor protein that the body cleaves into several distinct hormones and signaling molecules. This particular fragment spans positions 115 to 133 of the mouse POMC sequence and falls within the CLIP (Corticotropin-Like Intermediate Lobe Peptide) region, which is released during the processing of ACTH. The stored sequence, RPVKVYPNVAENESAEAFP, is the mouse-derived form and has been used as a synthetic research tool to study the MC2R melanocortin receptor. It is not an approved drug or therapeutic compound.
What it does
POMC is processed into different peptide products depending on the tissue: in the anterior pituitary it primarily yields ACTH, while in other regions the ACTH precursor is further cleaved into α-MSH and CLIP-related fragments (Harno and colleagues, Physiological Reviews 2018). The [115-133] fragment sits in this CLIP region. MC2R — the receptor it is assigned to — is a class A GPCR expressed predominantly in the adrenal cortex, where it mediates ACTH-stimulated cortisol production. Research into the melanocortin receptor family, including MC2R, has been motivated in part by its potential relevance to degenerative and inflammatory conditions (Cai and colleagues, Current Protein & Peptide Science 2016).
Evidence
- Human: No human clinical data for this specific POMC fragment.
- Animal: The sequence RPVKVYPNVAENESAEAFP was identified as a POMC/CLIP fragment in quantitative peptidomics of mouse pituitary tissue, comparing wild-type and carboxypeptidase E-deficient (Cpefat/fat) mice; the study measured relative abundance of this and related POMC-derived peptides across genotypes (Che and colleagues, Journal of Mass Spectrometry 2005).
- In vitro: No in vitro bioactivity data for this specific fragment are present in the current dossier.
Mechanism
MC2R is the only melanocortin receptor with strict selectivity for ACTH — it does not respond to the shorter melanocortin peptides (α-MSH, β-MSH, γ-MSH) that activate MC1R, MC3R, MC4R, and MC5R. The receptor signals through Gαs-coupled cAMP elevation in adrenocortical cells, driving steroidogenesis. POMC-derived melanocortin peptides as a class have been shown to act through distinct cellular mechanisms compared to glucocorticoid steroids despite overlapping anti-inflammatory effects in some contexts (Clemson and colleagues, Ocular Immunology and Inflammation 2017). The broader melanocortin receptor system, which spans MC1R through MC5R, has been examined as a target for multiple degenerative disease indications (Cai and colleagues 2016).
Related peptides
The POMC precursor gives rise to a family of biologically active fragments that are covered in separate platform cards. ACTH (corticotropin) is the immediate upstream precursor containing this CLIP region. α-MSH, which activates MC1R and MC3R–MC5R but not MC2R, is another well-studied POMC-derived melanocortin.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does the rigid proline end-cap make this peptide occupy the cortisol receptor without switching it on, blocking ACTH from doing so?
If this fragment naturally blocks the receptor that drives cortisol production, it could inspire a new drug for Cushing disease, where the adrenal gland is over-stimulated and produces dangerously high cortisol. A treatment that blocks this receptor with a natural peptide scaffold could be safer than existing options.
If the ends of this peptide were chemically joined into a loop, would it become a stable, drug-like molecule that blocks excess cortisol production?
Macrocyclic peptides derived from natural human sequences tend to be safer and less likely to cause immune reactions than fully synthetic drugs. If this cyclization strategy works, it could yield a new treatment for Cushing disease or other conditions of cortisol excess, which currently have limited and often poorly tolerated drug options.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7344871759414673 | boltz-2 |
| ranking score | 0.792789101600647 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.796 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10636,
sequence = {RPVKVYPNVAENESAEAFP},
target = {mc2r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}