F tier · safety concern
There is no published study in which orexin B has been administered to a human being, and ClinicalTrials.gov holds zero registered studies of it; the sibling peptide orexin A has at least three small intranasal studies, so orexin B has strictly less human evidence than a compound already graded low. Radiolabelling work in mice found no intact orexin B in brain after peripheral injection because it is rapidly degraded in blood.
orexin-b
Orexin B is the shorter of the two neuropeptides cleaved from prepro-orexin, acting as a full agonist at the OX2 receptor and a weaker agonist at OX1. It shares the arousal-regulating biology of orexin A but has been studied far less, and unlike orexin A it has never been given to humans in any published study. Its physical chemistry is also less favourable: it lacks the lipophilicity of orexin A and is degraded quickly in blood.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
Orexin B is the second of the two natural wake-promoting brain peptides. It has been studied much less than orexin A, and nobody has ever published a study of giving it to a person. In mice, injecting it into the bloodstream produced no detectable intact peptide in the brain because it broke down too fast.
regulatory status
Not an approved medicine anywhere; research reagent only
Orexin B has no marketing authorisation from the MHRA, EMA or FDA, is not a licensed medicinal product in the UK, and has never been the subject of a registered clinical trial; lawful supply is as a laboratory research reagent, not for human use. As with orexin A, the approved drugs in this pathway are receptor ANTAGONISTS — daridorexant is licensed and NICE-recommended for long-term insomnia in adults in England (TA922, October 2023) — so nothing about their approval transfers to an agonist peptide. Orexin B is not named on the WADA Prohibited List but falls within class S0 (Non-Approved Substances) as a pharmacological substance with no current approval by any governmental regulatory health authority for human therapeutic use, prohibited at all times. It is not an authorised food supplement ingredient in the UK.
how it works · proposed mechanism
Prepro-orexin is cleaved to give two peptides, orexin A and orexin B, which together signal through two G protein-coupled receptors identified in the same 1998 paper. Orexin B is the shorter, unbridged peptide and is the more OX2-weighted of the two ligands. OX2R is the receptor subtype most closely tied to wake maintenance and to cataplexy, which is why OX2R-selective agonism has become the focus of orexin replacement research.
Receptor profile: OX2-preferring, not OX2-exclusive
In the IUPHAR/BPS Guide to Pharmacology, both orexin A and orexin B are recorded as full agonists at OX2R across a comparable potency range, whereas at OX1R the ranking is orexin A greater than orexin B. Orexin B is therefore best described as relatively OX2-preferring rather than selective. It is not a clean pharmacological tool for isolating OX2 signalling.
It does not reach the brain from blood
In mice, orexin A entered brain from blood rapidly by simple diffusion, while no intact radiolabelled orexin B could be detected in brain after peripheral injection. Orexin B had a far lower octanol/buffer partition coefficient and was rapidly degraded in blood. For a peptide whose targets are hypothalamic and brainstem, that is a first-order obstacle.
No human administration data at all
Every published human study of an orexin peptide used orexin A, intranasally, in narcolepsy. Orexin B has never been administered to a human being in a published study, and ClinicalTrials.gov holds no registered study of it. There is consequently no human pharmacokinetic, safety, tolerability or efficacy information of any kind.
The OX2R idea is being pursued without the peptide
The interest in OX2R agonism is well founded: oveporexton (TAK-861), an oral small-molecule OX2R-selective agonist, met all primary and secondary endpoints in two phase 3 narcolepsy type 1 trials enrolling 168 and 105 participants. That programme is evidence for the receptor as a target, not for orexin B as a drug, and it exists because the peptide route was not practicable.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Orexin B has less human evidence than almost anything in this index: not a small trial, not a case series, but literally nothing. No human has been given it in any published study and no trial of it has ever been registered. The two facts that are established about it both cut against use as a drug — it is degraded rapidly in blood with no intact peptide detectable in mouse brain after peripheral injection, and it is only relatively OX2-preferring rather than OX2-selective. Anything sold on the strength of orexin biology is trading on orexin A's three small intranasal studies and on a small-molecule agonist programme that does not involve this peptide at all.
key published findings
- ClinicalTrials.gov holds zero registered studies of orexin B / hypocretin-2 as an intervention; a registry search for hypocretin returns only receptor antagonists, observational biomarker studies and small-molecule agonists.
- Orexin A and orexin B were identified together as two peptides from one precursor activating two previously orphan G protein-coupled receptors, and centrally administered orexins stimulated food consumption in rats (Sakurai, Cell 1998).
- In mice, orexin A crossed from blood into brain rapidly by simple diffusion, but no intact orexin B could be detected in brain after peripheral injection, and orexin B was rapidly degraded in blood (Kastin and Akerstrom, J Pharmacol Exp Ther 1999).
- The IUPHAR/BPS Guide to Pharmacology records both peptides as full agonists at OX2R over a comparable potency range, with orexin A more potent than orexin B at OX1R — so orexin B is OX2-preferring, not OX2-selective.
- Human orexin B is residues 70–97 of prepro-orexin with a C-terminal methioninamide and, unlike orexin A, contains no disulfide bonds (UniProt O43612).
- Clinical validation of OX2R agonism came from an oral small molecule, oveporexton (TAK-861), which met all primary and secondary endpoints in phase 3 trials of 168 and 105 participants — not from the peptide.
limitations of the evidence
- There is no human evidence of any kind: no pharmacokinetics, no tolerability data, no efficacy data, no case reports.
- Peripheral administration is contradicted by the only relevant delivery study, which found the peptide degraded in blood and undetectable in brain.
- Orexin B has not been tested by the intranasal route that was used for orexin A, so even that indirect precedent does not apply.
- It is not receptor-selective enough to serve as a clean OX2R tool, which limits its value even as a laboratory reagent for that purpose.
- The published preclinical literature on orexin B is far smaller than on orexin A, so even animal dose-response and safety characterisation is thin.
- No pharmacopoeial monograph or reference standard exists, so identity and purity of material sold under this name are unverifiable.
documented safety signals
- No adverse events have ever been reported in humans because no human has ever been documented as receiving it; absence of reported harm here reflects a complete absence of study.
- Orexin receptor activation increases sympathetic outflow and arousal in animal models, so cardiovascular and autonomic effects are biologically plausible and entirely uncharacterised in humans.
- The peptide's rapid degradation in blood means systemic exposure generates fragment species whose activity and immunogenicity have not been studied.
- Unlicensed material has no identity, purity or endotoxin standard, and methionine at the amidated C-terminus is readily oxidised, so degraded product is a realistic risk.
identity
| full name | Orexin B (hypocretin-2), the 28-residue amidated neuropeptide processed from human prepro-orexin (HCRT) |
| category | Cognitive |
| modality | peptide |
| formula | C123H212N44O35S |
| molar mass | 2899.3 g/mol |
| cas | 205599-76-4 |
| sequence | RSGPPGLQGRLQRLLQASGNHAAGILTM-NH2 (28 aa; C-terminal methioninamide, no disulfide bonds; residues 70–97 of human prepro-orexin, UniProt O43612) |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C and protected from light. Once reconstituted, laboratory practice is refrigeration at 2-8 °C for short-term use, or aliquoting and freezing to avoid repeated freeze-thaw cycles. Handling information only; this material has no approved human use. |
| solubility | Short hydrophilic peptide, readily soluble in sterile or bacteriostatic water and in dilute aqueous buffer. Lot-specific solubility is stated on the certificate of analysis. |
| co-studied with | Not applicable. There are no human combination data, and pairing an orexin receptor agonist peptide with a licensed orexin receptor antagonist such as daridorexant would be directly pharmacologically opposed. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedClinicalTrials.gov, U.S. National Library of Medicine · 2026 · official
UniProt Consortium · 2026 · reference
PubChem, National Library of Medicine · 2026 · reference
Journal of Pharmacology and Experimental Therapeutics · 1999 · preclinical
Cell · 1998 · preclinical
IUPHAR/BPS Guide to Pharmacology · 2026 · reference
others in Cognitive