BRP

What is BRP?

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 sits between KK and KR cleavage sites in its 78-kDa secreted parent, mouse genetics suggest prohormone convertase 1 (PCSK1) is at least partly responsible for releasing it, only the C-terminally amidated form is active, and it is detectable endogenously in human cerebrospinal fluid at roughly 700 pM to 3 nM. Given as a drug, BRP reduces food intake by activating neurons in several hypothalamic nuclei (including the arcuate and dorsomedial nuclei) — but not the pro-opiomelanocortin (POMC) neurons often named in media coverage — through a mechanism that is independent of leptin, the GLP-1 receptor, and the melanocortin 4 receptor, unlike approved incretin and MC4R-targeted drugs. It was identified by the Svensson lab at Stanford using 'Peptide Predictor', a rule-based computer program that scans protein sequences for prohormone-convertase cleavage motifs, and published in Nature in March 2025. All published data is preclinical (mice, rats and minipigs); no human trial has been registered as of October 2026.

What BRP Is Investigated For

BRP is investigated as a non-incretin anti-obesity peptide that targets the same downstream outcome as semaglutide — appetite reduction and weight loss — but through a different upstream mechanism. In the published Nature work, a single injection (into the abdominal cavity in mice, into muscle in minipigs) cut food intake by 20–50% in mice and by 50% at one hour in minipigs, and 14 days of daily injections left obese mice about 4 g lighter than saline-treated controls (Stanford's press release described this as about 3 g lost versus 3 g gained), with the loss coming from fat rather than lean mass and alongside improved glucose and insulin tolerance. Critically for the 'natural Ozempic' framing that drives public interest: no conditioned taste aversion, no pica (a rat nausea proxy), no change in gastric emptying or fecal output, no muscle loss, and no movement changes or anxiety-like behavior were observed in the animal models. The caveats are substantial. Only preclinical data exists. The receptor BRP binds has not been identified (its signalling resembles a Gs-coupled GPCR driving cAMP-PKA-CREB-FOS, inferred from inhibitor experiments in cultured cells), and the neurons it acts on are POMC-negative cells whose identity is unknown. Its potency is low (about 30 µM for half-maximal activity in cells) and it lasts under 10 minutes in mouse plasma, so the authors say chemical optimization is needed before it could become a practical drug. No human trial has been registered, and no human efficacy or safety signal exists. Any 'BRP peptide' sold on the research-chemical market in 2026 is selling a compound that has not been tested in a single human and whose purity, provenance, and pharmacokinetics in humans are entirely unknown.

History & Discovery

BRP was identified by Laetitia Coassolo and colleagues in Katrin Svensson's laboratory at Stanford Medicine (Stanford's international patent application claims priority to August 2022, and the paper was submitted to Nature in August 2023), as part of a broader computational-functional program to identify previously uncharacterized bioactive peptides released from secreted proteins. The group's 'Peptide Predictor' program (regular-expression pattern matching rather than machine learning) screens the human secretome for the paired basic-residue motifs (KR, RR, RK, KK) that prohormone convertases cleave, producing a list of candidate peptide products that would be generated if the precursor protein were processed. Of 2,082 secreted human proteins scanned, 373 looked like prohormones and yielded 2,683 predicted peptides; 100 short candidates were synthesized and screened for Fos induction in neuronal and pancreatic cell lines, and the top hits were tested in feeding studies, and BRP — the 12-residue fragment of BRINP2 — emerged as the strongest non-incretin anti-obesity hit. The paper was published in Nature on 5 March 2025 (volume 641, issue 8061, pages 192–201) under the title 'Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide.' Svensson co-founded Merrifield Therapeutics to advance BRP toward human trials, and the discovery drew broad media attention in 2025 and 2026 under the 'natural Ozempic' framing — a useful shorthand for public audiences but an imprecise description of the underlying pharmacology. Both the receptor and the POMC-negative neurons BRP acts on remain unidentified, and the published work explicitly leaves them as future work. Nature Reviews Endocrinology and Nature Reviews Drug Discovery ran research highlights on the paper in spring 2025, but as of October 2026 no other laboratory has published a replication.

How It Works

BRP is a short natural peptide that your brain makes in small amounts. In animal studies, extra BRP switches on a group of appetite-regulating neurons in the hypothalamus. These are not the well-known POMC neurons, and BRP did not activate the brainstem, which the authors link to its lack of nausea-like effects. This reduces hunger and food intake, leading to fat loss — without the nausea-like responses that GLP-1 drugs trigger in the same animal tests. But this has only been tested in mice, rats and pigs so far; no one has tried it in humans yet.

BRP corresponds to amino acids 386–397 of BRINP2 (THRILRRLFNLC), flanked by KK and KR cleavage sites. Brain BRP was nearly absent in male, and 50–80% lower in female, mice carrying a PCSK1 mutation, suggesting prohormone convertase 1 (PCSK1) is at least partly responsible for releasing it. The active form carries a C-terminal amide; the non-amidated peptide had no activity in cells. The peptide is detectable in normal human cerebrospinal fluid at concentrations between ~700 pM and ~3 nM, indicating it is an endogenous signaling peptide and not merely a synthetic fragment. Injected BRP raised FOS (a marker of neuronal activation) in the dorsomedial, preoptic, tuberal and arcuate nuclei of the hypothalamus but not in the hindbrain or brainstem. The activated arcuate cells did not co-stain for POMC; the authors describe them as POMC-negative neurons of unknown identity. In cultured neuronal cells, BRP's signalling resembled a Gs-coupled G-protein-coupled receptor (identity unresolved): it elevates intracellular cAMP, activating protein kinase A (PKA), which phosphorylates the transcription factor CREB, driving FOS expression and neuronal activation. A single leucine (Leu8) was required for this signalling. In metabolic cages, BRP-treated mice ate fewer meals with longer gaps between them, not smaller meals. Their respiratory exchange ratio fell, suggesting a shift toward burning fat, but oxygen consumption (a measure of energy expenditure) did not change, so eating less is the main driver of the weight loss. Critically, the published work shows that BRP's anti-obesity effect is independent of the three best-characterized appetite pathways (tested with a GLP-1 receptor-blocking drug, leptin-deficient ob/ob mice and Mc4r-knockout mice; GLP-1 receptor knockout mice were not used): leptin signaling, the GLP-1 receptor (the target of semaglutide/tirzepatide and the full incretin class), and the melanocortin 4 receptor (the target of setmelanotide). This places BRP in a 'non-incretin' anti-obesity category distinct from the approved incretin and MC4R drugs. The authors' proposed explanation for the lack of nausea-like responses is that BRP activates the hypothalamus but not the brainstem; it also did not change gastric emptying in mice. Given together with GLP-1 in mice, the two had additive effects on food intake, consistent with parallel pathways. Beyond the brain, BRP also activated a pancreatic beta-cell line in the original screen, so effects in other tissues cannot be ruled out.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about BRP:

• 01Receptor and cell identity — the receptor BRP binds (presumed, not proven, to be a Gs-coupled GPCR) and the POMC-negative hypothalamic neurons it activates have not been identified. Until they are, target engagement, off-target profiling, and structure-activity relationship work are materially constrained.
• 02Human efficacy and safety — zero human administration data exists. The jump from rodent and minipig results to human efficacy is where most anti-obesity candidates fail.
• 03Pharmacokinetics in humans — half-life, clearance, bioavailability by subcutaneous vs other routes, and distribution are unstudied.
• 04Durability of weight loss — whether BRP-driven weight loss plateaus, rebounds on discontinuation, or translates into long-term metabolic improvement is unknown.
• 05Tolerance on chronic dosing — repeated exposure did not desensitize cultured cells, and mice kept responding over 14 days, but longer dosing has not been studied.
• 06Head-to-head comparison vs modern GLP-1 drugs — the paper compared BRP only with liraglutide and native GLP-1 in mice and minipigs (liraglutide gave greater initial weight loss in obese mice). There is no comparison with semaglutide or tirzepatide in any species.
• 07Potency and half-life — BRP needed about 30 µM for half-maximal activity in cells, milligram-per-kilogram doses in animals, and left mouse plasma in under 10 minutes; the authors say chemical optimization is needed before it could be a practical drug.
• 08Physiological role — injected BRP is enough to cause weight loss, but whether the body's own BRP regulates appetite, and how its levels change with fasting or overeating, is unknown.
• 09Independent replication — as of October 2026 no other laboratory has published a replication of the BRP feeding results.
• 10Interaction with approved anti-obesity drugs, including combination potential with incretin agonists.

Forms & Administration

In the published preclinical work, BRP was given by intraperitoneal injection in mice and intramuscular injection in minipigs; it also suppressed feeding in mice when given intranasally or directly into the brain. Its half-life in mouse plasma was under 10 minutes, and only the C-terminally amidated form was active, which matters for anyone evaluating a vendor product. It is not available through any approved human-use channel. Reference-grade synthetic BRP is sold by specialty biochemistry suppliers for in vitro and animal research; any human use of such material is not supported by any human safety data and is not an authorized route. No approved human formulation, dose, or dosing schedule exists.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

BRP is not FDA-approved, has no human safety or efficacy data, and is not intended for human use outside of a registered clinical trial. This section describes the published animal dosing framework for reference only — it is not a human protocol.

Common Questions

Who BRP Is NOT For

Drug & Supplement Interactions

No formal interaction studies have been conducted in humans. Theoretical considerations, all unvalidated: combined use with GLP-1 or dual/triple incretin agonists would stack two appetite-suppressive pathways — in mice, BRP plus native GLP-1 suppressed food intake more than either alone, but no combination has been tested in humans; combined use with setmelanotide is untested (BRP still worked in Mc4r-knockout mice, so the two appear to act on separate pathways); and anti-hyperglycemic medications would require glucose monitoring given the preclinical improvement in glucose tolerance. Any concurrent medication use should be disclosed to the prescribing clinician in any future BRP trial.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions