Side-by-side · Research reference
PE 22-28vsTB-500
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED16/47 cited
BPhase 2HUMAN-REVIEWED8/46 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
TB-500
Thymosin β4 fragment · Healing
SQ or IM · Multiple sites · 2–3×/week
01Mechanism of Action
Parameter
PE 22-28
TB-500
Primary target
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
G-actin (sequestering) + cell-surface integrinsGoldstein 2012
Pathway
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Actin remodelling → cell migration; integrin-linked signaling → angiogenesis; anti-inflammatory cytokine modulationGoldstein 2012Malinda 1999
Downstream effect
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Accelerated wound healing, endothelial migration, hair follicle regeneration, cardiac repair (preclinical)Goldstein 2012
Feedback intact?
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Endogenous protein at baseline; supplementation amplifies
Origin
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
17-AA active fragment of endogenous 43-AA thymosin β4 (TMSB4X gene)Goldstein 2012
Antibody development
Not reported in animal studies
—
02Dosage Protocols
Parameter
PE 22-28
TB-500
Animal dose (antidepressant)
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
—
Animal dose (neuroprotection)
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
—
Frequency
Once daily
Sustained antidepressant effect over 7+ days.
2× per week (loading); then 1× per week (maintenance)
Onset (animal)
Within hours (acute); full effect 4–7 days
—
Comparison to fluoxetine
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
—
Human equivalent (extrapolated)
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
—
Evidence basis
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Animal-strong + Phase 2 dermal/ocular trialsGoldstein 2012
Standard dose
—
2 mg per injectionGoldstein 2012
Anecdotal community range; clinical Phase 2 trials used 70–840 mcg/kg IV.
Lower / starter dose
—
1 mg per injection
Duration
—
4–8 weeks loading; longer maintenance for chronic injury
Reconstitution
—
Bacteriostatic water, 1–2 mL per 5 mg vial
Timing
—
Evening or pre-rest preferred (anecdotal)
Half-life
—
~2 hours (estimated; tissue uptake longer)
04Side Effects & Safety
Parameter
PE 22-28
TB-500
Toxicity (animal)
No adverse effects reported at therapeutic doses
—
Cardiovascular (theoretical)
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
—
Weight change
Not reported in animal studies
—
Neurological
No seizures or behavioral abnormalities noted
—
Long-term safety
Unknown — longest animal study 28 days
Unknown beyond Phase 2
Injection site reaction
—
Mild erythema, transient pain
GI symptoms
—
Rare nausea (anecdotal)
Cancer risk
—
Theoretical via angiogenesis pathway
Lethargy / fatigue
—
Reported anecdotally during loading phase
Antibody formation
—
No data (no long-term human trials)
Pregnancy / OB
—
Avoid
Absolute Contraindications
PE 22-28
- ·Human use — no clinical safety data available
TB-500
- ·Active malignancy (theoretical angiogenesis concern)
- ·Pregnancy / breastfeeding
Relative Contraindications
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
TB-500
- ·Cancer history
- ·Concurrent VEGF inhibitor therapy
05Administration Protocol
Parameter
PE 22-28
TB-500
1. Animal protocol (IP)
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
Add 1–2 mL bacteriostatic water to 5 mg vial → 2.5–5 mg/mL. Roll gently.
2. Stability
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
SQ near injury site (preferred), or systemic SQ (abdomen). Rotate sites.
3. BBB penetration
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
Evening or pre-sleep is most common anecdotal timing.
4. Human formulation
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
Lyophilised: room temp, light-protected. Reconstituted: refrigerate, ≤30 days.
5. Needle
—
27–31G, 4–8 mm insulin syringe.
06Stack Synergy
PE 22-28
— no documented stacks
TB-500
+ BPC-157
StrongTB-500 and BPC-157 cover complementary halves of tissue repair: BPC-157 upregulates VEGFR2-driven angiogenesis and fibroblast outgrowth; TB-500 sequesters G-actin to enable endothelial / epithelial migration. The anecdotal canonical "healing stack" — pairs especially well for tendon and ligament injuries.
- TB-500
- 2 mg SQ · 2× per week
- BPC-157
- 250–500 mcg SQ · daily
- Primary benefit
- Combined angiogenesis + cell migration for tendon/ligament/muscle repair