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 is cleaved from its 78-kDa secreted parent by prohormone convertase 1 (PCSK1) at flanking KK/KR recognition sites and is detectable endogenously in human cerebrospinal fluid at roughly 700 pM to 3 nM. BRP reduces food intake by activating 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 distinct pharmacological class from every currently approved anti-obesity drug. It was identified computationally by the Svensson lab at Stanford using their 'Peptide Predictor' pipeline and published in Nature in March 2025. All published data is preclinical (mice and minipigs); no human trials have begun as of this writing.

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 subcutaneous injection reduced food intake by up to 50% within one hour in lean mice and minipigs, and 14 days of daily dosing in obese mice produced ~3 g of fat-selective weight loss versus ~3 g of weight gain in controls, alongside improved glucose and insulin tolerance. Critically for the 'natural Ozempic' framing that drives public interest: no nausea, constipation, muscle loss, movement changes, or anxiety-like behavior were observed in the animal models. The caveats are substantial. Only preclinical data exists. The specific receptor that BRP binds on POMC neurons has not been identified (it is a GPCR activating cAMP-PKA-CREB-FOS but its molecular identity is unresolved). No human trials have been initiated, 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 in early 2025 by Laetitia Coassolo and colleagues in Katrin Svensson's laboratory at Stanford Medicine, as part of a broader computational-functional program to identify previously uncharacterized bioactive peptides released from secreted proteins. The group's 'Peptide Predictor' pipeline screens the human secretome for sequences flanked by KK and KR motifs that prohormone convertases are known to cleave, producing a list of candidate peptide products that would be generated if the precursor protein were processed. Of approximately 20,000 human protein-coding genes scanned, 2,683 putative cleavage products were prioritized; around 100 were synthesized and screened in cellular assays and 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.' Following publication, Svensson co-founded Merrifield Therapeutics, a Stanford spin-out dedicated to advancing 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. The receptor target on POMC neurons remains unidentified, and the published work explicitly leaves its molecular identification as future work.

How It Works

BRP is a short natural peptide that your brain makes in small amounts. In animal studies, giving extra BRP directly turns up the activity of a cluster of appetite-regulating neurons called POMC neurons in the hypothalamus. This reduces hunger and food intake, leading to fat loss — all without the nausea that GLP-1 drugs like Ozempic typically cause. But this has only been tested in mice and pigs so far; no one has tried it in humans yet.

BRP is released from the parent protein BRINP2 when prohormone convertase 1 (PCSK1) cleaves the precursor at KK and KR recognition sites flanking amino acids 386–397, yielding the 12-residue sequence THRILRRLFNLC. 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. In the arcuate hypothalamus, BRP selectively activates POMC neurons. The downstream signaling cascade has been characterized: BRP binding at a hypothalamic G-protein-coupled receptor (molecular identity still unresolved as of the original Nature publication) elevates intracellular cAMP, activating protein kinase A (PKA), which phosphorylates the transcription factor CREB, driving FOS expression and neuronal activation. POMC neurons project to thermogenic and appetite-regulatory circuits, and their activation simultaneously reduces food intake and may increase fat oxidation — the dual outputs that drive fat-selective weight loss in the preclinical data. Critically, the published work demonstrates that BRP's anti-obesity effect is independent of the three best-characterized appetite pathways: 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 distinct pharmacological category — a 'non-incretin' anti-obesity peptide — that has no currently approved member. The absence of GI tract signaling engagement is the proposed explanation for the absence of nausea and constipation observed in animal models.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about BRP:

• 01Receptor identity — the specific GPCR that BRP binds on POMC neurons has not been identified. Until it is, 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 or receptor desensitization on chronic dosing — not characterized.
• 06Head-to-head comparison vs GLP-1 agonists — the 'natural Ozempic' framing is premature; no comparative efficacy data in any species exists.
• 07Interaction with approved anti-obesity drugs, including combination potential with incretin agonists.

Forms & Administration

In the published preclinical work, BRP was administered by subcutaneous injection. 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, and some research-chemical-market vendors have begun offering it to the public following media coverage — this use 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 and is untested; combined use with setmelanotide would involve two drugs acting on overlapping POMC-MC4R circuitry and is untested; 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