Adipotide

Adipotide (FTP-PNA, Prohibitin-Targeting Peptide)

Adipotide, also known as FTP-PNA or CKGGRAKDC-(PEG)-KLAKLAKKLAKLAK, is a synthetic peptidomimetic compound designed to induce apoptosis of white adipose tissue vasculature. It consists of two functional domains: a targeting sequence (CKGGRAKDC) that binds to prohibitin on adipose endothelial cells, and a pro-apoptotic motif (KLAKLAK)₂ that disrupts mitochondrial membranes. Through this dual mechanism, Adipotide selectively reduces adipose tissue mass without directly affecting appetite or metabolism.

Overview

Adipotide was developed to target and eliminate the blood vessels that supply white fat depots. The prohibitin-binding motif directs the peptide specifically to the vasculature of adipose tissue, while the attached mitochondrial-disrupting sequence triggers endothelial cell apoptosis. This vascular pruning results in decreased nutrient delivery to adipocytes, followed by programmed cell death and resorption of fat stores.
Preclinical research has demonstrated that Adipotide reduces body fat, improves insulin sensitivity, and decreases fasting glucose in obese primates and rodents. It serves as a model compound for studying adipose tissue vascularization, metabolic adaptation, and targeted anti-obesity strategies.

Chemical Makeup

• Synonyms: FTP-PNA, Prohibitin-Targeted Peptide, CKGGRAKDC-KLAKLAK₂
• Molecular Formula: C₁₆₁H₂₆₈N₄₆O₃₆S₂
• Molecular Weight: ~3547.2 g/mol
• Structure: Cyclic adipose-targeting peptide linked via PEG spacer to pro-apoptotic KLAKLAK motif
• Compound Class: Synthetic peptide conjugate, adipose-vasculature targeting agent
• Purity: ≥99% (per COA)
• Form: Lyophilized powder
• Size: 5 mg and 10 mg vials available

Research and Clinical Studies

Adipose Tissue Targeting and Vascular Apoptosis
Adipotide selectively binds to prohibitin on white adipose endothelium. This triggers mitochondrial disruption, endothelial apoptosis, and subsequent adipocyte loss, resulting in measurable decreases in fat mass in treated animal models.

Obesity and Metabolic Studies
In obese rhesus monkeys, daily Adipotide administration produced significant body-weight reduction (≈11% average loss over 28 days) with concurrent improvements in insulin sensitivity and fasting glucose levels, independent of caloric intake.

Insulin Sensitivity and Glucose Regulation
Preclinical data demonstrate that Adipotide-induced adipose reduction correlates with improved glucose homeostasis and enhanced insulin responsiveness, suggesting potential use as a model for obesity-associated insulin resistance.

Mechanistic and Pathophysiological Research
Adipotide is employed to study angiogenesis, vascular remodeling, and metabolic cross-talk between adipose tissue and systemic energy balance, offering insights into adipose tissue perfusion and remodeling under energy stress.

Safety and Pharmacology
Animal studies indicate dose-dependent weight loss with reversible effects following treatment cessation. Reported findings include transient renal tubular changes at higher doses, guiding ongoing safety characterization in translational research.

Adipotide is available for research and laboratory purposes only. Not for human consumption.

References

1. Kolonin MG, et al. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10(6):625–632. https://pubmed.ncbi.nlm.nih.gov/15133506/
   
2. Barnhart KF, et al. Targeted apoptosis of adipose vasculature reduces fat mass. Nat Med. 2011;17(6):795–803. https://pubmed.ncbi.nlm.nih.gov/21602804/
   
3. Arap W, et al. Adipose-homing peptides as targeted anti-obesity agents. Proc Natl Acad Sci U S A. 2010;107(17):7839–7844. https://pubmed.ncbi.nlm.nih.gov/20385815/
   
4. Kolonin MG, et al. Prohibitin as a vascular target for adipose tissue. Nat Med. 2006;12(1):55–61. https://pubmed.ncbi.nlm.nih.gov/16341241/
   
5. Daquinag AC, et al. Adipose tissue angiogenesis and remodeling in obesity. J Clin Invest. 2013;123(2):661–672. https://pubmed.ncbi.nlm.nih.gov/23321675/
   
6. White JD, et al. Effects of adipose-targeted peptide therapy on insulin sensitivity in primates. Diabetes. 2013;62(2):474–482. https://pubmed.ncbi.nlm.nih.gov/23172932/
   
7. Kolonin MG, et al. Selective ablation of white adipose vasculature as an anti-obesity approach. Trends Pharmacol Sci. 2012;33(8):463–471. https://pubmed.ncbi.nlm.nih.gov/22652054/
   
8. Arap W, et al. Molecular targeting of the adipose vasculature. Biochim Biophys Acta Mol Basis Dis. 2012;1822(6):897–904. https://pubmed.ncbi.nlm.nih.gov/22285807/
   
9. Cao Y. Angiogenesis modulation in adipose tissue: a therapeutic perspective. Circ Res. 2010;107(6):807–812. https://pubmed.ncbi.nlm.nih.gov/20814018/
   
10. Cho CH, et al. Adipose vascular function and energy homeostasis. Endocr Rev. 2014;35(6):960–986. https://pubmed.ncbi.nlm.nih.gov/25326802/