Adipotide
Emerging researchProhibitin-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.
Molecular & research data
- Sequence
- CKGGRAKDC-GG-D(KLAKLAK)2
- Molecular weight
- N/A
- Half-life
- Not established
- Routes (research)
- Injectable
- Storage
- Lyophilized: -20°C freezer. Reconstituted: 2-8°C refrigerated
Overview
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 research findings
- 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
Research applications
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.
Adipotide FAQ
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
- [1]A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeysReference
- [2]Reversal of obesity by targeted ablation of adipose tissueReference
- [3]Prohibitin/Annexin A2 Interaction Regulates Fatty-Acid TransportReference
- [4]Mixed-Chirality Prohibitin Peptide: D-(RLARLAR)2 Enhances StabilityReference
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Last reviewed: 2026-06-26. Information is provided for research and educational reference only — see our disclaimer.