Spexin: appetite-suppressing hormone (SPX/Neuropeptide Q)
A natural hormone that reduces hunger and food intake; low levels are linked to obesity and type 2 diabetes in humans, but no approved drug or human trial exists yet, research only.
- Class
- Peptide hormone; GALR2/GALR3 agonist
- Status
- No approved therapeutic; research molecule only
- Best-supported effect
- Reduced food intake and body weight in rodent and non-human primate models (preclinical); circulating spexin inversely associated with obesity, T2D, and MAFLD in human observational studies (biomarker association only — not therapeutic evidence)
- Main caveat
- No human therapeutic trial of exogenous spexin has been registered or completed; observational biomarker data do not establish therapeutic causality
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: Peptide hormone; GALR2/GALR3 agonist
Evidence tier: Animal-only evidence
Status: No approved therapeutic; research molecule only
Best-supported effect: Reduced food intake and body weight in rodent and non-human primate models (preclinical); circulating spexin inversely associated with obesity, type 2 diabetes, and MAFLD in human observational studies (biomarker association only)
Main caveat: No human therapeutic trial of exogenous spexin has been registered or completed; observational biomarker data do not establish therapeutic causality
What this is
Spexin (also called SPX or neuropeptide Q / NPQ) is a 14-amino-acid amidated peptide hormone encoded by the C12ORF39 gene on chromosome 12. It was identified in 2007 through a bioinformatic screen of the human genome for unannotated secreted peptides, and was subsequently shown to selectively activate galanin receptor 2 (GalR2) and galanin receptor 3 (GalR3) while not activating GalR1 — an unusual selectivity within the galanin family. Spexin is expressed broadly across the brain (especially the hypothalamus and brainstem), pancreas, adipose tissue, gastrointestinal tract, gonads, kidney, and heart. In humans, circulating spexin is consistently lower in people with obesity, type 2 diabetes, MAFLD, and polycystic ovary syndrome, and rises after weight loss or bariatric surgery. This pattern has generated interest in spexin as both a metabolic biomarker and a candidate therapeutic — but as of 2026, no approved spexin drug exists, no clinical trial of exogenous spexin has been registered, and no human pharmacokinetic or efficacy data are available.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Observational only | Multiple cohort studies associate reduced circulating spexin with obesity, T2D, MAFLD, and related conditions; levels rise with weight loss and bariatric surgery. No human therapeutic trial of exogenous spexin identified. Observational associations do not establish therapeutic causality. |
| Animal | Moderate | Consistent preclinical evidence across rodent and non-human primate models: central or peripheral administration of exogenous spexin reduces food intake, body weight, and adipocyte long-chain fatty acid uptake, and improves glucose tolerance in diet-induced obesity models. Evidence base is growing but small relative to validated obesity drug targets. |
| In vitro | Moderate | GalR2 and GalR3 receptor binding and selectivity characterized pharmacologically; adipocyte fatty acid uptake inhibition demonstrated in cell-based assays. GalR1 non-activation is a key pharmacological distinction. |
| Computational | None identified | No platform structure prediction or docking data attached. |
| Mechanism | Moderate to strong | GalR2/GalR3 selectivity is well characterized; receptor-knockout studies support connection to energy metabolism. Whether selective GalR2/GalR3 activation is sufficient for clinically meaningful weight loss in humans remains an open question. |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Reduces food intake and body weight | Supported (preclinical) | Animal | Medium — consistent across rodent and NHP models; no human therapeutic data |
| Circulating spexin is reduced in obesity and metabolic disease | Supported (observational) | Human — observational | Medium — multiple independent cohort studies; causality direction not established |
| Exogenous spexin produces weight loss in humans | Not established | Human | High — no completed or registered human therapeutic trial identified |
| Effective alternative to approved GLP-1 drugs for weight loss | Not established | None | High — no human efficacy data; comparison with semaglutide or tirzepatide is not supportable from current evidence |
| Improves glucose tolerance | Supported (preclinical) | Animal | Medium — diet-induced obesity rodent models; human therapeutic evidence absent |
| Cardiovascular and renal protection | Weak (preclinical) | Animal | Low — described in preclinical models; not a primary evidence focus; no human data |
Experimental exposure
This section reports exposure used in animal experiments and in vitro assays. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Rodent central administration | Rodent (arcuate nucleus) | Intracerebroventricular injection of synthetic spexin | Acute and short-term | Food intake, orexigenic neuropeptide expression | Central route; not a feasible clinical administration route |
| Rodent peripheral administration | Rodent, diet-induced obesity model | Subcutaneous or intraperitoneal injection of synthetic spexin | Study-specific; exact duration not individually extracted | Body weight, adipocyte fatty acid uptake, glucose tolerance, plasma lipids | No human pharmacokinetic or translation data |
| Non-human primate model | Non-human primate | Peripheral spexin administration; exact dose and regimen not individually extracted in source | Study-specific | Food intake, body weight | Limited species; no human equivalence established |
| Adipocyte assay | Isolated adipocyte cell preparation | Spexin at study-specific concentrations | Assay-specific timepoint | Long-chain fatty acid uptake inhibition via GalR2 | In vitro; does not establish systemic exposure context |
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| No human adverse event database | Not applicable | No approved product; no human clinical safety dataset for exogenous spexin |
| Potential behavioral and endocrine off-target effects | Preclinical (rodent, proposed mechanism) | Preclinical GalR2 effects on anxiety circuits (amygdala) and reproductive hormone secretion are pharmacologically active; chronic systemic activation has not been characterized for psychiatric or endocrine off-target effects in any species |
| Cardiovascular effects | Preclinical | Reduced heart rate and blood pressure reported in some rodent models; clinical implications in humans not established |
| Research-chemical product quality | per available sources | Research-chemical "spexin" products sold online have no human pharmacokinetic, safety, or purity data; published literature explicitly describes this as an unvalidated grey-market context |
| Long-term effects of chronic GalR2/GalR3 activation | Not established | Tolerance, immunogenicity, and cardiovascular, reproductive, and behavioral off-target effects have not been characterized for chronic systemic dosing in any system |
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved | Not approved for any indication; not a scheduled substance; no active IND on record as of source reporting |
| EU | Not approved | Per available sources, no EU approval; no registered clinical trial in the EU identified |
| UK, Japan, Australia, Canada | Not approved | Per available sources, no approval in these jurisdictions as of 2026 |
| WADA | Not specifically named on Prohibited List | Source notes that as an unapproved peptide with effects on metabolism, body composition, and potentially hormone secretion, it could fall under WADA catch-all categories for non-approved substances; status is per available sources and has not been independently verified in this card |
| Research / compounding | Research molecule only | No established clinical or compounding pathway; available only through unregulated research-chemical channels |
No approved therapeutic status identified. This card describes a research molecule, not an approved medicine.
Mechanism
Spexin acts as a selective agonist at galanin receptor 2 (GalR2) and galanin receptor 3 (GalR3), both Gi/Go-coupled G protein-coupled receptors (GPCRs), with low nanomolar affinity. It does not activate GalR1 — a pharmacological selectivity that distinguishes it from galanin itself, which activates all three subtypes. This selectivity is central to spexin's distinct pharmacology and is well characterized in receptor binding studies.
In the central nervous system, spexin is expressed in the hypothalamus and brainstem, and central administration in rodents suppresses food intake and reduces orexigenic neuropeptide expression in the arcuate nucleus. In peripheral tissue, GalR2 activation on adipocytes inhibits the uptake of long-chain fatty acids. In diet-induced obesity rodent models, peripheral spexin administration improves glucose tolerance and reduces plasma lipids. Additional preclinically described effects include modulation of cardiovascular function, anxiolytic behavior (via GalR2 in the amygdala), antinociception, modulation of reproductive hormone secretion, and effects on gastrointestinal motility.
Spexin is encoded as a 116-amino-acid preproprotein by the C12ORF39 gene on chromosome 12; the mature circulating form is the C-terminally amidated 14-amino-acid peptide. Its expression is broad — brain, pancreas, adipose tissue, gastrointestinal tract, gonads, kidney, and heart — consistent with its proposed roles across multiple physiological systems.
Whether selective GalR2/GalR3 activation is sufficient to produce clinically meaningful weight loss in humans, and whether the proposed mechanisms translate across species, remain open questions.
Chemistry
| Field | Value |
|---|---|
| Sequence (notation, SB/CU sources) | H-NWTPQAMLYLKGAQ-NH2 |
| Length | 14 amino acids |
| Topology | Linear |
| Modifications | C-terminal amidation (–NH2); N-terminal free amine (H–) |
| Molecular weight | Not reported in available literature |
| Formula | Not reported in available literature |
| CAS | Not reported in available literature |
| Gene | C12ORF39 (chromosome 12); preproprotein: 116 amino acids |
| Sequence confidence | Needs review — see note below |
Sequence note: Two sequence representations appear in the available literature. The chemistry and common-use sections give the 14-residue amidated sequence H-NWTPQAMLYLKGAQ-NH2, consistent with the stated "14-amino-acid" identity throughout published research. The mechanism section gives NWTPQAMLYDLKGAQ, which is 15 residues and contains an apparent additional aspartate (D) at position 10. The 14-residue form is the dominant and consistently labeled version; the 15-residue form appears to contain an extraneous residue. Both are preserved here; the 14-residue form is used as the primary sequence. This discrepancy should be verified against the primary literature before publication.
Open questions
- Human therapeutic translation: No human clinical trial of exogenous spexin administration has been registered or completed for any indication. Whether preclinical effects on food intake, body weight, and glucose tolerance translate to humans is the central unknown.
- Human pharmacokinetics: Half-life, bioavailability, and effective plasma concentration of exogenous spexin in humans are unknown. No human pharmacokinetic data are identified.
- GalR2/GalR3 sufficiency: Whether selective GalR2/GalR3 activation alone is sufficient for clinically meaningful weight loss in humans, or whether additional receptor engagement or polypharmacology is required, has not been established.
- Long-term safety of chronic GalR2/GalR3 activation: Chronic systemic dosing effects on mood, anxiety, reproductive function, pain perception, cardiovascular function, and immunogenicity have not been characterized in any species for extended durations.
- Biomarker vs therapeutic causality: Reduced circulating spexin in obesity, T2D, and MAFLD is consistently observed, but the causal direction is unresolved — whether low spexin drives disease progression or is a consequence of metabolic dysregulation has not been established.
- Antifibrotic and cardiometabolic mechanisms: Whether spexin's antifibrotic and cardiometabolic effects in preclinical models reflect direct GalR2/GalR3 pharmacology or secondary effects of improved metabolic state is unclear.
- Drug development path: Whether a small-molecule GalR2/GalR3 agonist is a more viable therapeutic development path than the peptide itself has not been resolved.
- Sequence discrepancy: A minor sequence discrepancy between source sections (14 vs 15 residues) requires verification against primary chemistry literature before publication.
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 spexin bind its receptor in a way that suppresses hunger without causing the receptor to switch off over time?
If true, spexin-based drugs could avoid the tachyphylaxis (wearing off) that has undermined many previous appetite suppressants, offering more durable weight management for people with obesity.
Does spexin directly prevent liver scarring cells from activating, on top of its role in suppressing appetite?
If true, spexin or its analogs could become the first drug to simultaneously reduce body weight and slow fatty liver progression, benefiting the large population where both problems co-occur.
Does spexin activate survival signals in brain cells that could reduce damage during a stroke?
If true, spexin could be repurposed as a neuroprotective agent given alongside clot-busting therapy in stroke, potentially reducing lasting disability for stroke survivors.
Does one amino acid difference at the beginning of spexin explain why it does not trigger the brain receptor that causes drowsiness?
If true, this would give drug designers a clear rule for making spexin-like molecules that suppress appetite without causing sedation or memory problems, a major obstacle for galanin-based drugs.
Would swapping the one vulnerable amino acid in spexin for a chemically tougher version preserve its activity while making it last long enough to work as a drug?
If true, a simple chemistry fix could move spexin from a fragile research molecule to a stable drug candidate for obesity or metabolic disease, reducing the cost and complexity of development.
▸3-letter notation
▸citationbibtex
@peptide{pep10962,
sequence = {NWTPQAMLYLKGAQ},
target = {},
author = {peptidemodel},
year = {2026},
status = {designed}
}