PE-22-28 is a cognitive & neuro research compound currently in stock directly from a verified Chinese manufacturer. Every batch is tested by the manufacturer for purity and concentration as part of routine quality control. Sourcing is direct — no intermediaries. Minimum order value is $600 USD. International shipping available.
PE-22-28 is a synthetic heptapeptide corresponding to residues 22–28 of spinorphin — a naturally occurring opioid-modulating peptide derived from the β-chain of haemoglobin. Spinorphin was first characterised as an endogenous inhibitor of enkephalin-degrading enzymes and as a delta opioid receptor modulator, but subsequent research identified PE-22-28 specifically for an independent and mechanistically distinct activity: selective binding to FKBP51 (FK506-binding protein 51), a co-chaperone of Hsp90 involved in glucocorticoid receptor (GR) regulation and HPA axis stress signalling. This FKBP51-targeting activity positions PE-22-28 in a distinct pharmacological category from both opioid peptides and classical anxiolytics, making it a research tool for the growing field of FKBP51-modulated stress-response biology.
FKBP51 is a critical regulator of the stress axis. It binds the glucocorticoid receptor in the Hsp90 chaperone complex and reduces GR sensitivity to cortisol, thereby modulating the feedback regulation of the HPA axis. Elevated FKBP51 expression — associated with polymorphisms in the FKBP5 gene — is a validated risk factor for PTSD, major depression, and anxiety disorders in genetic epidemiology studies. By inhibiting FKBP51 through its FK506-binding domain (FKBD1), PE-22-28 is investigated for its ability to enhance GR sensitivity, accelerate HPA axis recovery after stress, and produce anxiolytic and antidepressant-like outcomes in preclinical models — without engaging classical opioid or GABAergic pathways.
PeptidesFromChina.co supplies PE-22-28 as a lyophilized powder at 10 mg per vial, synthesized to ≥98% purity verified by HPLC and confirmed by mass spectrometry. Every batch is tested by the manufacturer for purity and concentration as part of routine quality control. All products are intended for laboratory research use only and are not for human consumption.
| Chemical Class | Synthetic heptapeptide; spinorphin fragment (residues 22–28) |
|---|---|
| Parent Peptide | Spinorphin (haemoglobin β-chain derived opioid-modulating peptide) |
| Primary Target | FKBP51 (FK506-binding protein 51) — FKBD1 domain |
| Molecular Weight | ~880 Da (7-residue peptide) |
| Research Areas | FKBP51 inhibition, HPA axis modulation, glucocorticoid receptor sensitisation, stress/anxiety/depression research, PTSD biology |
| Mechanism | FKBP51 ligand → enhanced GR sensitivity → HPA axis feedback modulation |
| Form | Lyophilized powder |
| Storage | −20°C; protect from light and moisture |
| Name | Strength | Pack Size | Purity | Availability | Price (USD) |
|---|---|---|---|---|---|
| PE-22-28 | 10 mg | 10 vials | ≥98% | In Stock | $111.00 |
Testing method: HPLC / LC-MS. Every batch is tested before shipment. Purity ≥99% confirmed per batch.
Every batch is tested by the manufacturer for purity and concentration as part of routine quality control, using methods such as HPLC and LC-MS. These results are kept in the manufacturer's internal quality-control records and are not issued as a separate certificate or document.
PE-22-28's binding to the FKBP51 FKBD1 domain is characterised by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC), yielding Kd values in the low-micromolar range in published studies. In cell-free chaperone assays, PE-22-28 displaces the Hsp90–FKBP51 interaction with the glucocorticoid receptor (GR) complex, releasing GR from the low-affinity FKBP51-stabilised state. Functional GR translocation assays (GR–GFP nuclear accumulation following dexamethasone stimulation) in FKBP51-overexpressing HEK-293 or corticotrope cell lines confirm that PE-22-28 restores GR nuclear translocation efficiency at concentrations consistent with its binding affinity. Chromatin immunoprecipitation (ChIP) assays downstream of PE-22-28 treatment characterise resulting changes in GR-target gene expression (GILZ, SGK1, FK506-binding regulatory targets) as markers of GR sensitisation.
The HPA axis research context for PE-22-28 is directly linked to the FKBP5 genetic risk literature for PTSD and depression. FKBP51 is transcriptionally induced by GR activation (a negative feedback amplifier), and elevated basal FKBP51 expression in FKBP5 risk-allele carriers delays GR nuclear translocation and prolongs cortisol release after stress. In rodent models, chronic social defeat stress and unpredictable mild stress (UCMS) protocols are used to characterise the effect of PE-22-28 on post-stress corticosterone recovery (measured by serial plasma sampling after acute restraint stress), ACTH dynamics, and CRH expression in the paraventricular nucleus. FKBP51 knockout mouse comparisons provide a genetic benchmark for the maximum achievable pharmacological HPA axis effect via FKBP51 inhibition.
PE-22-28 is evaluated in standard rodent behavioural models used to characterise anxiolytic and antidepressant potential. Elevated plus maze (EPM), open field test (OFT), and light-dark emergence box characterise anxiolytic activity. Forced swim test (FST), sucrose preference test (SPT for anhedonia), and novelty suppressed feeding (NSF) assess antidepressant-relevant endpoints. PE-22-28 is distinguished from benzodiazepine anxiolytics (which produce sedation and motor impairment in these models) and from SSRIs (which require chronic dosing in the FST protocol) by its FKBP51-mediated mechanism. Comparison protocols pairing PE-22-28 with FKBP5 knockout animals, FKBP5 siRNA knockdown, or FKBP51 inhibitor controls establish whether the behavioural effects are on-target. The compound's lack of direct opioid receptor involvement is confirmed by naloxone pre-treatment experiments, which do not abolish the anxiolytic phenotype.
The genetic epidemiology linking FKBP5 polymorphisms to PTSD risk — particularly the interaction between childhood trauma exposure and FKBP5 rs1360780 genotype in predicting adult PTSD susceptibility — has established FKBP51 as one of the most genetically validated molecular targets in stress psychiatry research. PE-22-28 is used in fear extinction and fear renewal models (auditory cue-dependent fear conditioning followed by extinction training) to characterise whether FKBP51 inhibition facilitates extinction memory consolidation and reduces fear renewal — a key mechanism implicated in PTSD treatment resistance. Glucocorticoid receptor signalling in the basolateral amygdala and hippocampus during extinction learning is measured by in situ hybridisation and quantitative immunohistochemistry to define the brain regions where PE-22-28 exerts its extinction-facilitating effects.
FKBP51 (encoded by the FKBP5 gene) is a co-chaperone that binds the Hsp90-glucocorticoid receptor (GR) complex and reduces GR sensitivity to cortisol. This creates a brake on HPA axis negative feedback: when FKBP51 is highly expressed, GR is less responsive, cortisol stays elevated longer after stress, and the HPA axis recovers slowly. FKBP5 single nucleotide polymorphisms (particularly rs1360780) that increase FKBP51 expression are strongly associated with PTSD risk, major depression, and impaired stress recovery in large human genetic studies. Pharmacological inhibition of FKBP51 — as studied with PE-22-28 — is investigated as a way to enhance GR sensitivity and normalise HPA axis function as a potential mechanism for stress-related disorder intervention.
Spinorphin is an endogenous heptapeptide derived from the β-chain of haemoglobin with known activity as an enkephalin-degrading enzyme inhibitor and delta opioid receptor modulator. PE-22-28 corresponds to residues 22–28 of spinorphin and retains part of the parent peptide's primary structure, but its FKBP51 inhibitory activity represents a distinct pharmacological property independent of the opioid modulating effects of the full spinorphin sequence. PE-22-28 is therefore studied as a selective FKBP51 research tool rather than as an opioid-pathway compound.
Classical anxiolytics (benzodiazepines, buspirone, SSRIs) act via GABA-A receptor positive allosteric modulation, 5-HT1A agonism, or serotonin reuptake inhibition respectively. PE-22-28 acts through FKBP51 inhibition and downstream GR sensitisation — entirely upstream of monoamine neurotransmitter systems. It does not bind GABA-A, serotonin, or opioid receptors directly, and its anxiolytic activity in rodent models is not blocked by flumazenil (benzodiazepine antagonist) or naloxone (opioid antagonist). This mechanistic distinctiveness makes PE-22-28 a useful comparator in research designs that aim to dissect neuroendocrine versus direct neurotransmitter contributions to anxiolytic endpoints.
PE-22-28 is supplied as lyophilized powder at ≥98% purity, verified by HPLC and confirmed by mass spectrometry. Vials contain 10 mg. Every batch is tested by the manufacturer for purity and concentration as part of routine quality control. Certificates of Analysis are available on request.
For laboratory research use only. Not for human or veterinary use. PeptidesFromChina.co is a B2B wholesale supplier operating under strict research-use-only terms. All products are sold exclusively for in vitro and preclinical research purposes.