Adipotide
Prohibitin-Targeting Peptidomimetic | Experimental Anti-Obesity
Chimeric adipose-vasculature-targeted peptidomimetic targeting prohibitin/annexin A2 on white adipose tissue endothelium, delivering pro-apoptotic D-(KLAKLAK)2 motif. In obese primates it produced rapid fat loss with improved insulin resistance, yet development halted after Phase 1 due to kidney safety signals.
Mechanism of Action
CKGGRAKDC ligand homes to prohibitin/annexin A2 on white-fat endothelium; linked D-(KLAKLAK)2 disrupts mitochondrial membranes post-internalization, triggering localized endothelial apoptosis and adipocyte loss.
Key Benefits
- Rapid fat-mass reduction via selective white adipose tissue vascular targeting
- Improved insulin sensitivity following adipose reduction
- Non-CNS peripheral mechanism distinct from appetite suppressants
CKGGRAKDC-GG-D(KLAKLAK)2 Complex or non-standard sequence format
Weight Loss
- Adipose Mass Reduction
Selective white adipose tissue vascular targeting produced 7-15% body-weight loss over 4 weeks in obese macaques.
Metabolic
- Insulin Resistance
Improved insulin response (reduced insulin AUC) following fat-mass reduction in primates.
Appetite Control
- Non-CNS Mechanism
Weight loss without primary appetite suppression; peripheral vascular approach.
Rapid fat-mass reduction in obese non-human primates with improved insulin sensitivity; direct white adipose tissue vascular targeting.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Primate Research Replication | 0.43 mg/kg | Once daily | SubQ |
| Dose-Finding (Research) | 0.10-0.75 mg/kg | Once daily (escalating tiers) | SubQ |
Reconstitution Instructions
- Lyophilized peptide vial
- Bacteriostatic water (BAC water)
- Alcohol swabs & sterile syringes
- Insulin syringes (0.5-1 mL)
- 1 Sanitize hands and workspace; swab vial septum
- 2 Inject BAC water slowly down vial wall; do not jet onto powder
- 3 Gently swirl until fully dissolved (do not shake)
- 4 Label with concentration/date; store at 2-8°C
Potential additive dehydration/GI effects; monitor renal function.
Overlapping weight-loss effects; monitor kidney function, volume status, electrolytes.
No clinical data on co-administration; mechanisms differ.
No published data on combined use or pharmacodynamic interaction.
No known direct interaction; distinct mechanisms and targets.
Metabolic effects may confound body-composition endpoints.
Theoretical vascular/pressor effects; stagger dosing, monitor BP and hydration.
Adipotide shows dose-dependent proximal tubule injury; avoid additional renal insults.
Early reduction in abdominal circumference
Progressive weight/fat-mass decline
Partial rebound possible; lab signals include mild creatinine rise and electrolyte shifts
Common Side Effects
- Mild creatinine elevation
- Electrolyte shifts
- Dose-dependent proximal tubule changes (reversible in primates)
Stop Signs - Discontinue if:
- Sustained creatinine elevation or oliguria
- Progressive electrolyte abnormalities
- Severe injection-site reactions or systemic symptoms
- Unexpected toxicity
Contraindications
- Pregnancy/lactation (not studied)
- Dehydration
- Concurrent nephrotoxic medications
Good Signs
- Intact lyophilized cake - white, uniform indicates proper lyophilization
- Clear solution - fully dissolved, particle-free after reconstitution
Warning Signs
- Minor clumping may form from shipping; should dissolve with gentle swirl
Bad Signs
- Collapsed/moist cake suggests temperature excursion; do not use without QC
- Cloudiness/precipitate indicates degradation or contamination—discard
- A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys(2011)
Rhesus macaques at 0.43 mg/kg SC daily for 28 days showed 7.4-14.7% weight loss; insulin resistance improved; mild, dose-dependent, reversible proximal tubule changes.
- Reversal of obesity by targeted ablation of adipose tissue(2004)
Mice with diet-induced obesity showed ~30% weight reduction; adipose vascular apoptosis; metabolic normalization.
- Prohibitin/Annexin A2 Interaction Regulates Fatty-Acid Transport(2016)
Mechanistic validation of prohibitin/ANXA2 axis in adipose tissue, core to TP01 targeting.
- Mixed-Chirality Prohibitin Peptide: D-(RLARLAR)2 Enhances Stability(2025)
Next-generation prohibitin constructs improve serum stability and efficacy vs. first-generation TP01.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.