Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Adipotide is a synthetic chimeric peptide formally designated CKGGRAKDC-GG-(D)(KLAKLAK)₂ and sometimes called FTPP (Fat-Targeting Pro-apoptotic Peptide) or Prohibitin-Targeting Peptide 1. It links two functional sequences:
- CKGGRAKDC — a homing motif identified by phage-display library screening that binds prohibitin on the endothelial cells of white adipose tissue.
- (KLAKLAK)₂ — a pro-apoptotic peptide that disrupts mitochondrial membranes once internalized.
When the chimera reaches white-fat capillaries, the homing sequence localizes it to prohibitin-positive endothelial cells; the apoptotic warhead then triggers cell death in the adipose vasculature. Loss of vascular supply leads to involution of the surrounding white fat. The compound was designed as an exploratory pharmacology tool for obesity research, not as a routine therapeutic.
History
The work originated in the Arap and Pasqualini laboratories at MD Anderson Cancer Center. The original Nature Medicine paper (Kolonin et al., 2004) reported that the homing motif identified in vivo phage-display screens of mouse adipose tissue, when fused to the pro-apoptotic warhead, produced rapid reduction in adipose mass and reversal of obesity in mouse models.
Subsequent work in 2011 (Barnhart et al., Science Translational Medicine) demonstrated dose-dependent weight loss and improved insulin sensitivity in obese rhesus macaques over a four-week course of subcutaneous injections. A Phase I human trial in obese men was reported in 2012, conducted by Ablaris Therapeutics — the company spun out of MD Anderson to develop the compound. Development effectively stalled after that trial; the published primate data noted renal monitoring findings and reversible histological changes in kidney tissue, and human renal safety questions were a frequent topic of subsequent commentary.
Regulatory status
Adipotide has no regulatory approval in any jurisdiction. It is not on any FDA bulks list. The 2012 Phase I trial in humans is the most advanced clinical work; no Phase II program has been published. Development at Ablaris was wound down, and no successor company has restarted clinical work. The compound is occasionally listed by research-chemical vendors labeled not for human use.
Mechanism
The compound's selectivity depends on two requirements:
- Prohibitin expression on adipose vasculature. Prohibitin is normally an intracellular mitochondrial-membrane protein but is also displayed on the endothelial surface of white-fat capillaries. The CKGGRAKDC sequence binds this surface-displayed prohibitin and concentrates the peptide at adipose vessels.
- Internalization and apoptosis. Once bound, the chimera is internalized; the (KLAKLAK)₂ warhead disrupts the mitochondrial inner membrane in the endothelial cells, triggering apoptosis.
Loss of vascular supply causes secondary involution of the adipose tissue. The mechanism is fundamentally pro-apoptotic — the design intention is selective tissue destruction, not metabolic modulation. This is the source of the toxicity concern: prohibitin is also present in renal tissue, and renal effects have been observed in both primate and human studies.
Half-life and dosing intervals
Published estimates from the rodent and primate work put the circulating half-life at approximately 2–4 hours. In the Barnhart 2011 monkey study, the peptide was administered subcutaneously daily for four weeks; doses reached 0.4 mg per kilogram per day in the higher arms. The 2012 Phase I human trial reported by Ablaris used a similar daily subcutaneous schedule over a shorter course.
There is no established or approved human dose. Given the abandoned development status and the renal safety signal, the published doses should be regarded as historical exposure references, not as a basis for present use.
Reconstitution example
Adipotide is supplied through research-chemical vendors as a lyophilized powder, commonly in 10 mg vials. A 10 mg vial reconstituted with 2 mL of bacteriostatic water yields a concentration of 5 mg/mL. On a 1 mL U-100 insulin syringe, 10 units (0.10 mL) delivers 0.5 mg.
These figures describe vendor-supplied research material. The compound is not produced as a sterile injectable for therapeutic use by any approved manufacturer.
What to know
- Abandoned development. Adipotide has not advanced beyond the 2012 Phase I obesity trial. The renal safety signal in primate work and concerns raised in human follow-up are the principal reasons.
- Renal toxicity signal. The Barnhart 2011 primate paper documented reversible renal histological changes and elevated creatinine at higher doses. Human renal safety questions were not resolved in the published Phase I work.
- Pro-apoptotic mechanism. Unlike incretin or amylin peptides, Adipotide is designed to selectively destroy a target tissue. The mechanism is not metabolic; it is cytotoxic with a homing-driven selectivity that has limits.
- Storage. Refrigerate lyophilized vials and protect from light. Reconstituted solution stability has not been characterized in published data.
- Reported adverse events. Animal and human data describe renal effects; vendor-supplied research material has no approved safety profile.
Sources
- 1.Kolonin MG et al. (2004). Reversal of obesity by targeted ablation of adipose tissue. Nature Medicine.
- 2.Barnhart KF et al. (2011). A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Science Translational Medicine.
- 3.Staquicini FI et al. (2011). Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. PNAS.