Side-by-side · Research reference
AdipotidevsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED15/49 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
Adipotide
Pro-apoptotic Vascular-Targeting Peptide · Preclinical Only
IV · Systemic · Preclinical Protocols OnlyHossen 2013
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Adipotide
PE 22-28
Primary target
Prohibitin-1 (PHB1) on adipose vasculature endotheliumHossen 2013
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
CKGGRAKDC domain binds PHB1 → Peptide internalisation → D(KLAKLAK)₂ mitochondrial membrane disruption
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Endothelial apoptosis → Adipose vascular collapse → Adipocyte involution → Weight loss
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
Feedback intact?
N/A — Direct apoptotic mechanism, non-hormonal
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Synthetic bioconjugate: PHB1-targeting homing peptide + pro-apoptotic KLA sequence
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
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
Adipotide
PE 22-28
Animal dose (mouse)
Low dose (not specified in abstract)Hossen 2013
Systemic injection in diet-induced obesity (DIO) models.Hossen 2013
—
Route
Intravenous (systemic injection)
—
Frequency
Not specified in available data
Once daily
Sustained antidepressant effect over 7+ days.
Evidence basis
Preclinical animal models only
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Human data
None — no clinical trials reported
—
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.
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.
03Metabolic / Fat Loss Evidence
Parameter
Adipotide
PE 22-28
Primary fat target
White adipose tissue (all depots)
—
Body weight reduction
Significant reduction in DIO miceHossen 2013
Absolute values not provided in abstract.
—
Leptin levels
Significant decrease
Parallel to adipose mass reduction.
—
Effect on adipocytes
Antiobesity effect on dysfunctional adipose cells (adipocytes + macrophages)Hossen 2013
—
Ectopic fat
Reduction in ectopic fat depositionHossen 2013
Marker of dysfunctional adipose tissue / metabolic syndrome.
—
Species tested
Obese rhesus monkeys, DIO mice
—
Human translation
Unknown — no clinical trials
—
04Side Effects & Safety
Parameter
Adipotide
PE 22-28
Safety profile
Unknown — preclinical data only
—
Vascular selectivity
Targets adipose vasculature; off-target vascular effects unknown
—
Apoptotic mechanism risk
Pro-apoptotic payload may affect unintended tissues if selectivity incomplete
—
Kidney / liver toxicity
Not reported in available data
—
Immunogenicity
Not assessed in available data
—
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
Absolute Contraindications
Adipotide
- ·Human use — not approved, no clinical safety data
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Adipotide
- ·Any condition requiring intact adipose-tissue vascularisation
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Adipotide
PE 22-28
1. Route
Intravenous injection (systemic) in preclinical models. No human protocols exist.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Formulation
Bioconjugate peptide. May also be encapsulated in nanoparticles (prohibitin-targeted nanoparticle formulation, KLA-PTNP, showed superior efficacy vs. free bioconjugate in mice).Hossen 2013
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Preclinical dosing
Low-dose systemic injection (exact dosing not specified in available abstract). Frequency and duration not detailed.Hossen 2013
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Not specified — likely requires peptide-grade lyophilised storage and reconstitution.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.