Adipotide (FTPP) – Proapoptotic Peptidomimetic Targeting Adipose Vasculature

Chemical Identity

Chemical Name: CKGGRAKDC–GG–AAKA–GGC–NH₂ (disulfide-cyclized)
Synonyms: Adipotide; FTPP; Prohibitin-targeted peptide; Fat-targeting peptide
Molecular Formula: C₈₄H₁₃₄N₂₄O₂₆S₄ (cyclic, disulfide-linked)
Molecular Weight: ~2096.3 g/mol
Sequence: CKGGRAKDC–GG–AAKA–GGC
CAS Number: N/A (research-only compound)
Structure Type: Chimeric cyclic peptidomimetic with disulfide bridge between Cys¹ and Cys⁹

Pharmacological Classification

Adipotide (FTPP) is a **proapoptotic peptidomimetic** that selectively targets **white adipose tissue vasculature** by binding to **prohibitin**, a mitochondrial surface receptor expressed on adipose endothelial cells. It induces targeted apoptosis and vascular disruption, resulting in fat mass reduction in animal models.

Mechanism of Action

• Targeted Vascular Binding: The peptide binds to prohibitin (PHB), which is overexpressed on the surface of endothelial cells supplying white adipose tissue.
• Mitochondrial Disruption: The apoptotic domain (AAKA–GGC) mimics BH3-only peptides and induces mitochondrial outer membrane permeabilization (MOMP).
• Selective Apoptosis: Disruption of mitochondrial integrity leads to cytochrome c release and caspase activation, resulting in apoptosis of adipose endothelial cells.
• Secondary Fat Loss: Vascular rarefaction causes local hypoxia, triggering lipolysis and adipocyte apoptosis due to nutrient deprivation.

Target Interaction Summary

Target	Biological Role	Effect of Adipotide
Prohibitin (PHB)	Mitochondrial membrane scaffold; expressed on adipose endothelium	Ligand-mediated internalization and cell-specific apoptosis
BCL2/BAX Pathway	Apoptotic signal regulation	MOMP induction and caspase cascade activation
Adipocyte Microvasculature	Blood supply for white adipose depots	Vascular rarefaction and local hypoxia

β-Arrestin Recruitment

Adipotide does not function through GPCR signaling and does not recruit β-arrestin. Its biological effect is mediated through direct mitochondrial membrane disruption and apoptosis induction in targeted endothelial cells.

Pharmacokinetics (Non-Dosing)

• Route of Administration: Subcutaneous or intravenous injection (preclinical use only)
• Absorption: Rapid systemic distribution after injection; accumulates in adipose vasculature
• Bioavailability: High via parenteral routes; not orally bioavailable
• Metabolism: Proteolytic degradation by serum peptidases; intracellular cleavage post-uptake
• Excretion: Renal and hepatic clearance of peptide fragments

Stability and Storage

• Form: Lyophilized powder (acetate or trifluoroacetate salt)
• Solubility: Water, saline, or mild acidic buffers (pH 4.5–6.0)
• Storage: –20°C dry; protect from light and oxidation
• Reconstitution: Use sterile bacteriostatic water; refrigerate reconstituted solution and use within 7–10 days

References

1. Kolonin MG, et al. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10(6):625–632.
2. Lin PH, et al. Prohibitin-targeted peptide induces white adipose tissue apoptosis and weight loss in obese primates. Sci Transl Med. 2010;2(18):18ra11.
3. Kolonin MG. Targeting the vasculature of adipose tissue. Curr Opin Investig Drugs. 2008;9(4):350–354.
4. PubChem – Prohibitin (PHB) Protein Target. PubChem