Adipotide

also known as: FTPP, Fat-Targeted Proapoptotic Peptide, Prohibitin-TP01

A preclinical concept that killed white adipose tissue by inducing vasculature apoptosis in obese rhesus monkeys — dramatic weight loss, but also nephrotoxicity that stopped it from advancing to humans.

A chimeric 29-amino-acid peptide developed by the Arap/Pasqualini lab at MD Anderson, combining a prohibitin-targeting sequence (homes to white adipose vasculature) with the pro-apoptotic D(KLAKLAK)2 sequence (disrupts mitochondrial membranes), designed to kill the blood vessels feeding fat tissue and thereby cause fat regression.

Mechanism of action

The CKGGRAKDC sequence binds prohibitin on the surface of endothelial cells specifically within white adipose tissue vasculature, concentrating the peptide there. The D(KLAKLAK)2 "killer" sequence then inserts into mitochondrial membranes of those endothelial cells, triggering apoptosis. Loss of the blood supply causes the downstream adipocytes to regress. The same prohibitin-targeting motif is also present in renal proximal tubule cells, which is the mechanistic origin of the nephrotoxicity.

Primary uses

Obesity research (preclinical)
Tumor-targeting peptide research (same technology platform)
Community use should be considered extremely dangerous given the documented primate nephrotoxicity

Typical dosing

preclinical historical: daily SC (primate studies) (subcutaneous)

No human dosing exists. Community use carries meaningful risk of acute kidney injury.

Regulatory status

Not approved. Strong preclinical data in obese rhesus monkeys (Barnhart et al., Sci Transl Med, 2011) showed ~11% body weight reduction and preferential fat loss over 28 days, but also produced nephrotoxicity (renal proximal tubule damage) in the monkey studies — which has prevented advancement into human trials despite enormous scientific interest.

References

[pubmed] Barnhart KF, et al. "A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys." Sci Transl Med, 2011;3:108ra112.
[pubmed] Kolonin MG, et al. "Reversal of obesity by targeted ablation of adipose tissue." Nat Med, 2004;10:625-632.

Related peptides

AOD-9604

A short GH fragment marketed heavily as a "fat-loss peptide" — but with a clinical record that has not supported meaningful weight loss in humans.

HGH Fragment 176-191

The lipolytic fragment that inspired AOD-9604 — binds a hypothesized non-GHR receptor to drive fat oxidation without growth-promoting effects, though human efficacy data are weak.

Tesofensine

A triple-monoamine reuptake inhibitor (SNDRI) with Phase 2 anti-obesity data showing up to ~12% weight loss at 1.0 mg/day — development stalled over cardiovascular concerns; not a peptide and included here for cross-reference only.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.