Adipotide

Overview

Adipotide (FTPP) is a chimeric peptidomimetic developed in the Arap/Pasqualini lab (originally at MD Anderson) that couples a 9-residue homing motif (CKGGRAKDC) — isolated by in vivo phage display as a ligand for prohibitin on white-adipose-tissue vasculature — to the D-amino-acid pro-apoptotic domain D(KLAKLAK)2. It is an experimental research compound, NOT FDA-approved for any indication. A clinical-development program in prostate-cancer-associated obesity reached early-phase testing and was ultimately discontinued.

Mechanism of Action

The CKGGRAKDC domain binds prohibitin, a mitochondrial/plasma-membrane protein enriched on white-adipose endothelium (Kolonin et al., Nat Med 2004). Upon receptor-mediated internalization, the attached D(KLAKLAK)2 amphipathic motif disrupts mitochondrial membranes and induces apoptosis of adipose-vascular endothelial cells. The resulting vascular pruning starves white adipose tissue of blood supply, driving adipocyte loss and weight reduction in preclinical models.

Research Summary

Foundational proof-of-concept in obese mice (Kolonin et al., Nat Med 2004, PMID 15133506). A 4-week dosing study in spontaneously obese rhesus macaques showed substantial body-weight and fat-mass loss and improved insulin sensitivity but produced dose-dependent renal proximal-tubule toxicity (Barnhart et al., Sci Transl Med 2011, PMID 22072637). A small Phase 1 trial in obese prostate-cancer patients was initiated and later terminated; the program was permanently discontinued. No published human efficacy data. Grey-market human use is unstudied and carries documented nephrotoxicity risk.

Dosing Information

Reported Side Effects

• Proximal-tubule nephrotoxicity (primate data)
• Dehydration
• Reduced appetite / nausea
• Fatigue
• Renal-function derangement requiring monitoring

Research References

• Reversal of obesity by targeted ablation of adipose tissue (Kolonin, Saha, Chan, Pasqualini & Arap, Nat Med 2004) (2004)
• A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys (Barnhart et al., Sci Transl Med 2011) (2011)