Brain Regeneration Peptide (BRP): experimental appetite-suppressing brain peptide
A small naturally occurring brain peptide that suppresses appetite and causes fat-focused weight loss in animal studies; experimental, not yet tested in humans.
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.
Snapshot
Class: Non-incretin POMC-activating endogenous hypothalamic peptide fragment
Evidence tier: Animal-only evidence
Status: Unapproved investigational peptide; no human trials initiated as of April 2026
Best-supported effect: Appetite suppression and fat-selective weight loss in rodent and minipig models (preclinical only)
Main caveat: No human dosing has occurred; the receptor mediating BRP's effect on POMC neurons has not been identified; all efficacy and safety data are from a single preclinical publication by one research group
What this is
BRP (BRINP2-Related Peptide) is a 12-amino-acid peptide with the sequence THRILRRLFNLC, corresponding to residues 386–397 of the human BRINP2 protein (BMP and retinoic acid inducible neural-specific 2). It is cleaved from its 78-kDa secreted precursor by prohormone convertase 1 (PCSK1) at flanking KK and KR recognition sites, and is detectable endogenously in human cerebrospinal fluid at approximately 700 pM to 3 nM — establishing it as a naturally occurring signaling peptide rather than a purely synthetic construct.
BRP was computationally identified by Laetitia Coassolo and colleagues in Katrin Svensson's laboratory at Stanford Medicine, using an AI-driven prohormone-cleavage prediction pipeline ("Peptide Predictor"), and published in Nature in March 2025. In animal studies, it activates pro-opiomelanocortin (POMC) neurons in the arcuate hypothalamus through a mechanism that is independent of leptin, the GLP-1 receptor, and the melanocortin 4 receptor — placing it in a pharmacological class distinct from all currently approved anti-obesity drugs. All published pharmacological data are preclinical; no human dosing has been reported.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Not present | No human pharmacological administration has occurred; endogenous BRP has been measured in human CSF, establishing biological presence but not therapeutic effect |
| Animal | Moderate | Acute food intake reduction (up to 50% within one hour) in lean mice and minipigs; fat-selective weight loss and improved glucose/insulin tolerance in obese mice after 14-day daily dosing; no nausea, muscle loss, or behavioral changes observed |
| In vitro | None identified | No cell assay or binding assay data are identified |
| Computational | Present / discovery-context | Identified via Peptide Predictor pipeline screening ~2,683 candidate prohormone cleavage products from ~20,000 human protein-coding genes; the computational step supported discovery, not binding or activity validation |
| Mechanism | Plausible | POMC/cAMP-PKA-CREB-FOS cascade characterized in preclinical work; GLP-1R, leptin, and MC4R independence demonstrated; specific upstream GPCR identity unresolved — primary mechanistic gap |
All animal evidence originates from a single primary publication (Nature, March 2025) by the Svensson laboratory at Stanford. Independent replication by other groups has not been reported in the available literature as of April 2026. This concentration of evidence in one research group is a key limitation of the current evidence base.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Appetite suppression and food intake reduction | Supported (animal) | Animal — rodent and minipig acute models | Medium — single publication; no independent replication reported in source |
| Fat-selective weight loss without muscle loss | Supported (animal) | Animal — obese mouse 14-day study | Medium — single publication; 14-day duration only; no human translation established |
| Anti-obesity effect is GLP-1-independent and MC4R-independent | Supported (animal) | Animal — mechanistic pharmacology in primary publication | Medium — demonstrated in preclinical models; therapeutic implications unstudied in humans |
| Improved glucose and insulin tolerance | Supported (animal) | Animal — obese mouse model, secondary endpoint | Medium — single publication; secondary to primary weight-loss endpoint |
| Absence of nausea, GI disturbance, or muscle loss | Supported (animal, short-protocol) | Animal — preclinical observation window only | Low — observed in short preclinical studies; cannot be extended to human tolerability; human side-effect profile is entirely unknown |
| Human efficacy for appetite suppression or weight loss | Not established | Human — no human dosing data present in source | High confidence in "not established" — no trial initiated as of April 2026 |
| Safety profile comparable to or better than GLP-1 agonists in humans | Not established | Human — no human data present | High confidence in "not established" — no comparative human data exists |
| "Natural Ozempic" equivalence with semaglutide | Not established | Animal / mechanistic | High — published literature explicitly demonstrates mechanism is GLP-1-independent; shared downstream behavioral output does not establish clinical equivalence, comparative efficacy, or comparable safety |
Experimental exposure
This section reports exposure used in animal experiments. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Animal experiment | Lean mice, subcutaneous injection | Single pre-meal injection; dose range not individually extracted from source | Acute (1-hour measurement) | Food intake reduction up to 50% vs vehicle | Rodent model; human-equivalent dose not established; no dose-response curve individually extracted |
| Animal experiment | Lean minipigs, subcutaneous injection | Single injection; dose not individually extracted from source | Acute | Reduced food intake | Single publication; no human translation established |
| Animal experiment | Obese mice, subcutaneous injection | Daily injections for 14 days; dose not individually extracted from source | 14 days | Fat mass reduction (~3 g vs ~3 g gain in vehicle controls); glucose and insulin tolerance improvement | Short duration; obese mouse model only; no chronic exposure data; no human translation established |
No approved human formulation, dose, or dosing schedule exists. No dose-response relationship has been established in any species. No human pharmacokinetic data exists.
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| No nausea or food aversion observed | Mice and minipigs — acute and 14-day studies | Favorable preclinical signal in short studies; does not establish human tolerability |
| No constipation or digestive changes observed | Mice — 14-day study | Favorable preclinical signal; short duration |
| No muscle loss observed | Obese mice — 14-day study | Short duration; human musculoskeletal effects are unstudied |
| No movement, water intake, or anxiety-like behavioral changes | Mice — standard behavioral battery | Standard preclinical battery; duration and species limits apply |
| Long-term POMC activation effects | Not characterized in any species | Sustained POMC stimulation effects, receptor downregulation, and compensatory pathway activation are unknown |
| Receptor off-target profile | Not assessable | The GPCR that BRP binds has not been identified; systematic off-target profiling is not possible until the receptor is known |
| Human pharmacokinetics | Not established | Half-life, clearance, bioavailability, and distribution in humans are entirely unstudied |
| Reproductive and developmental toxicology | Not established | No data in any species |
No human safety data of any kind is present in this card. The absence of adverse signals in short preclinical studies is a promising early indicator but does not constitute a human safety statement. Every anti-obesity agent that has reached approval had favorable animal tolerability before clinical trials revealed its full human side-effect profile.
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved; no IND publicly disclosed | Per available sources, no investigational new drug application filed as of April 2026; not a scheduled substance; research-chemical consumer sales exist but are not an authorized human-use channel. per available sources; not independently verified in this card. |
| EU (EMA) | Not authorized | Unapproved investigational peptide; no authorization in any EU member state. per available sources. |
| UK (MHRA), Canada, Australia, Japan | Not authorized | Per available sources, no authorization by any major regulatory authority globally. per available sources. |
| WADA | Not specifically listed; S2 coverage plausible | Per available sources, BRP has not been formally listed or ruled on by WADA as of April 2026; WADA S2 category ("Peptide Hormones, Growth Factors, Related Substances and Mimetics") plausibly covers BRP per source, but no formal ruling has been issued. per available sources; not independently refreshed in this card. |
No approved therapeutic status identified in the attached source. BRP is an early-stage investigational peptide with no authorized human-use channel in any jurisdiction.
Mechanism
BRP is cleaved from the secreted BRINP2 protein by prohormone convertase 1 (PCSK1), which recognizes KK and KR flanking motifs surrounding residues 386–397 of the 78-kDa precursor. The released 12-residue fragment (THRILRRLFNLC) is detectable endogenously in human cerebrospinal fluid at approximately 700 pM to 3 nM.
In the arcuate hypothalamus, BRP selectively activates POMC neurons. The intracellular signaling cascade downstream of BRP binding, as characterized in the primary Nature publication: receptor activation at an unidentified hypothalamic G-protein-coupled receptor (GPCR) elevates intracellular cAMP, activating protein kinase A (PKA), which phosphorylates the transcription factor CREB and drives FOS expression, producing neuronal activation. POMC neurons project to both appetite-suppressive and thermogenic/fat-oxidation circuits, which is consistent with the dual preclinical outputs of reduced food intake and fat-selective weight loss.
Mechanistic independence from approved appetite pathways: The published work demonstrates that BRP's anti-obesity effect is independent of leptin signaling, the GLP-1 receptor (the target of semaglutide and tirzepatide), and the melanocortin 4 receptor (the target of setmelanotide). The absence of GI-tract signaling engagement is the proposed mechanistic explanation for the absence of nausea in animal models. These conclusions are from preclinical models; human CNS pharmacology is unstudied.
Primary mechanistic gap: The molecular identity of the GPCR through which BRP acts has not been determined as of the original Nature publication. This gap materially constrains off-target profiling, structure-activity relationship work, and medicinal-chemistry optimization. Target confidence is inferred, not verified.
Chemistry
| Field | Value |
|---|---|
| Amino-acid sequence | THRILRRLFNLC |
| Length | 12 amino acids |
| Topology | Linear |
| Parent protein | BRINP2 (BMP and retinoic acid inducible neural-specific 2), human |
| Parent protein residues | 386–397 |
| Cleavage enzyme | Prohormone convertase 1 (PCSK1) |
| Cleavage recognition sites | Flanking KK and KR motifs |
| Endogenous CSF concentration | ~700 pM to ~3 nM (human, per available sources) |
| Modifications | None described; natural cleavage product |
| Molecular weight | Not individually extracted from source |
| Formula | Not individually extracted from source |
| CAS | Not present in source |
| Sequence confidence | Verified (primary source:) |
Open questions
- Receptor identification: The specific GPCR that BRP binds on hypothalamic POMC neurons has not been identified. Until this target is known, systematic off-target profiling, drug-drug interaction assessment, and structure-activity relationship optimization are materially constrained. This is the highest-priority mechanistic gap before human development can be fully designed.
- Human efficacy translation: No human pharmacological administration has occurred. The transition from rodent and minipig preclinical results to human anti-obesity efficacy is the primary translational barrier, and the point where most preclinical anti-obesity candidates fail.
- Human pharmacokinetics: Half-life, plasma clearance, bioavailability by subcutaneous and other routes, volume of distribution, and metabolite profile in humans are entirely unstudied. These parameters determine dosing interval, formulation approach, and trial design.
- Durability of weight loss: Whether BRP-induced weight loss is sustained, plateaus, or rebounds on discontinuation has not been characterized beyond the published 14-day rodent study.
- Tolerance and receptor desensitization: Whether chronic BRP dosing produces receptor downregulation, tachyphylaxis, or compensatory pathway activation is uncharacterized in any model.
- Comparative efficacy vs approved agents: No head-to-head comparison with GLP-1 agonists, tirzepatide, or setmelanotide has been conducted in any species. The "natural Ozempic" framing does not reflect comparative data.
- Independent replication: All published evidence derives from one paper by one research group. Independent laboratory replication of the core animal findings has not been reported in the available literature as of April 2026. This is a key robustness limitation of the current evidence base.
- Reproductive and developmental safety: No data in any species; a fundamental gap for any eventual human development program.
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.
Could this peptide suppress appetite through a different pathway than Ozempic, so people who respond poorly to Ozempic might still benefit from BRP?
Millions of people on GLP-1 drugs lose less weight than hoped. A drug working through a different brain circuit could be added on or used as an alternative, expanding effective treatment to a much larger group of patients with obesity.
Does this appetite-suppressing peptide only work if it can cross from the bloodstream into the brain, and if so, does a standard injection actually get it there?
If BRP can barely enter the brain after a standard injection, developers would need to design special delivery methods, such as a nasal spray, to make it clinically useful, potentially saving millions spent on ineffective injection trials.
Does this peptide reduce body fat specifically, without causing the muscle loss that many weight-loss treatments produce?
A treatment that selectively removes fat while preserving muscle would be far better than current options for people with obesity who need to protect their strength and mobility, especially older adults.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.6706521511077881 | openfold3-mlx |
| ranking score | 0.7805502414703369 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.479 | global PDE — lower = better |
| disorder | 0.150 | fraction disordered |
| chain pair ipTM (A, B) | 0.671 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 86s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10931,
sequence = {MTSSLFQTTSSSSNTLQ},
target = {neuroprotective},
author = {peptidemodel},
year = {2026},
status = {computed}
}