What is Adipotide?
Adipotide (FTPP, "fat-targeted pro-apoptotic peptide") is a chimeric peptidomimetic developed in the laboratories of Wadih Arap and Renata Pasqualini at MD Anderson Cancer Center. It was designed to selectively destroy the vasculature supporting white adipose tissue, with the goal of producing weight loss by eliminating fat stores at their blood supply rather than through appetite suppression or metabolic modulation.
Adipotide is not approved for any clinical use. Its single human Phase 1 trial in obese cancer patients was terminated in 2019 due to nephrotoxicity. Despite this safety failure, the peptide remains a topic of intense discussion in biohacker and "research peptide" communities, and is sold by some research chemical suppliers — buyers should be aware of the documented kidney toxicity that ended its clinical development.
Structure and Origin
Adipotide is a chimeric peptide combining two distinct functional domains:
- CKGGRAKDC — a homing motif identified by phage display that selectively binds prohibitin and annexin A2 receptors on white adipose tissue endothelium
- (GG linker)
- D-amino acid (KLAKLAK)2 — a pro-apoptotic peptide that disrupts mitochondrial membranes, triggering apoptosis when delivered intracellularly
The targeting motif concentrates the peptide at white adipose vasculature; the (KLAKLAK)2 domain then enters endothelial cells and induces apoptosis, killing the blood supply to fat depots and causing fat-pad regression.
Mechanism of Action
- Vascular targeting — CKGGRAKDC binds prohibitin/annexin A2 on white adipose endothelial cells (these markers are differentially upregulated in white fat vs other tissues)
- Endothelial apoptosis — internalized (KLAKLAK)2 disrupts mitochondrial membranes
- Loss of adipose vascular supply — adipocytes lose their blood supply and undergo apoptosis or atrophy
- Net fat-depot regression — measurable reduction in white adipose mass without direct effects on appetite or metabolism
Animal Evidence
Mouse and obese monkey studies (Nature Med 2004, Sci Transl Med 2011):
- Daily SC dosing produced dose-dependent weight loss in obese rodents and rhesus monkeys
- Up to 11% weight reduction in monkeys over 4 weeks
- Reduced adipose mass (preferentially abdominal/visceral)
- Improved insulin sensitivity in metabolically obese animals
- Brown adipose tissue and lean mass largely preserved
These data drove substantial interest and a Phase 1 trial.
Phase 1 Trial and Termination
A Phase 1 trial in obese cancer patients (NCT01700595) was initiated in 2012. The trial was terminated in 2019 after observation of nephrotoxicity (acute kidney injury):
- Renal vasculature shares some markers with adipose vasculature, leading to off-target accumulation
- The (KLAKLAK)2 domain is non-selectively cytotoxic once internalized
- The therapeutic index in humans was not adequate to support continued development
No subsequent clinical development has been reported.
Why It's Still Discussed
Despite the clinical failure, adipotide remains in active research use because:
- The vascular-targeting concept is generalizable to other tissues and indications
- The CKGGRAKDC motif is being studied for delivery applications
- It is sold by some research chemical suppliers as a "research peptide" for laboratory use
- It is heavily discussed in biohacker forums (r/Peptides) and longevity media as a "fat-targeting" peptide
This is an important caveat: people considering self-experimentation with adipotide should understand that the documented human nephrotoxicity is not theoretical — it ended a properly-conducted clinical trial. Any human use would be expected to carry significant risk of acute kidney injury.
Status
- Approved: No
- Active sponsor: None
- Clinical development: Terminated 2019
- Research use: Continues in academic settings; available from research chemical suppliers