Adipotide (Prohibitin-TP01)
Prohibitin-Targeting Peptidomimetic | Experimental Anti-Obesity
Community Research
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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.
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.
Molecular Data
CKGGRAKDC-GG-D(KLAKLAK)2 Complex or non-standard sequence format
Research Indications
Selective white adipose tissue vascular targeting produced 7-15% body-weight loss over 4 weeks in obese macaques.
Improved insulin response (reduced insulin AUC) following fat-mass reduction in primates.
Weight loss without primary appetite suppression; peripheral vascular approach.
Dosing Protocols
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
Interactions
What to Expect
Side Effects & Safety
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
Quality Checklist
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
Frequently Asked Questions
How does Adipotide's weight loss mechanism differ from semaglutide?
Adipotide targets adipose tissue vascular endothelium directly, causing localized endothelial apoptosis and adipocyte loss via a peripheral vascular mechanism. Semaglutide suppresses appetite centrally via GLP-1 receptors. Adipotide achieves weight loss without appetite suppression, making it mechanistically distinct from appetite suppressants.
What kidney safety concerns halted Adipotide's Phase 1 development?
Phase 1 trials showed dose-dependent mild creatinine elevation and reversible proximal tubule changes in kidney tissue. Although these effects reversed in primates, the kidney safety signals were considered significant enough to halt further clinical development. This remains a major concern for any consideration of Adipotide use.
How much weight can Adipotide actually produce?
In obese rhesus macaques, 0.43mg/kg SC daily for 28 days produced 7.4-14.7% body weight loss with improved insulin sensitivity. However, primate studies don't guarantee equivalent human efficacy, and the kidney safety signals prevented human Phase 2 trials from determining real-world dose-response in people.
Can I combine Adipotide with semaglutide for enhanced weight loss?
No combination data exists, and stacking has theoretical risks. Both would drive rapid weight loss and dehydration. Adipotide shows dose-dependent kidney effects, and semaglutide users already face dehydration/GI issues. Combined use requires careful monitoring of renal function, electrolytes, and hydration status, best avoided without specialist supervision.
References
- 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.
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Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.