Peptide Schedule
Adipotide (FTPP)9 residuesCKGGRAKDCEach bubble = one amino acid. Size = residue mass. Color = chemical class.Adipotide (FTPP)
Benefits
About Adipotide (FTPP)
Adipotide, also known as FTPP (Fat-Targeted Proapoptotic Peptide) or Prohibitin-TP01, is a synthetic peptidomimetic designed to selectively destroy the blood vessels that supply white adipose tissue. It consists of two functional domains: a cyclic homing peptide (CKGGRAKDC) that binds to prohibitin on the surface of adipose tissue endothelial cells, and a proapoptotic sequence D(KLAKLAK)2 that disrupts mitochondrial membranes once internalized, triggering programmed cell death in those endothelial cells. When the vasculature feeding fat depots is destroyed, the downstream adipocytes are starved of oxygen and nutrients, leading to fat cell death and tissue resorption. In preclinical mouse studies published in Nature Medicine in 2004, adipotide reversed diet-induced obesity by approximately 30% over four weeks. In a 2011 primate study published in Science Translational Medicine, obese rhesus monkeys treated with adipotide for 28 days lost 7-15% of body weight, with a 38% reduction in total body fat and a 27% reduction in abdominal fat as confirmed by MRI and DEXA. Insulin resistance also improved significantly. However, the same primate studies revealed dose-dependent renal injury, with kidney lesions ranging from minimal to moderate depending on dose level. Arrowhead Research initiated a Phase 1 human trial in 2012, but it was terminated due to unacceptable nephrotoxicity. The therapeutic window between effective fat-reducing doses and kidney-damaging doses proved too narrow for safe clinical use, and all clinical development was permanently discontinued in 2019. Adipotide remains one of the most striking examples of a research compound that achieved dramatic efficacy but could not overcome its own toxicity profile. It is not approved by any regulatory agency and is available only as a research chemical.
Who Should Consider Adipotide (FTPP)
- Research subjects in supervised preclinical settings only
- Not recommended for any unsupervised human use due to nephrotoxicity
- Animal models of obesity and adipose tissue biology
- Investigators studying vascular-targeted drug delivery
- Researchers exploring prohibitin as a therapeutic target
How Adipotide (FTPP) Works
Adipotide is a chimeric peptidomimetic composed of two functional domains connected by a glycine-glycine linker. The N-terminal homing domain (CKGGRAKDC) is a cyclic peptide originally identified through in vivo phage display screening that selectively binds to prohibitin (PHB), a multifunctional membrane protein expressed on the luminal surface of endothelial cells lining the blood vessels of white adipose tissue. Prohibitin forms a trimolecular complex with annexin A2 (ANXA2) and CD36 on the surface of these endothelial cells, regulating fatty acid transport from the bloodstream into fat tissue. Upon binding to prohibitin, adipotide is internalized into the endothelial cell via receptor-mediated endocytosis. The C-terminal proapoptotic domain, D(KLAKLAK)2, is a synthetic amphipathic D-amino acid peptide that resists proteolytic degradation. Once inside the cell, this domain localizes to the mitochondrial membrane, where its amphipathic structure allows it to insert into and disrupt the mitochondrial outer membrane, collapsing the membrane potential and triggering the intrinsic apoptotic cascade (cytochrome c release, caspase activation). The targeted apoptosis of endothelial cells destroys the microvasculature supplying white adipose tissue. Without blood supply, the downstream adipocytes undergo ischemic cell death and are gradually resorbed. The nephrotoxicity is attributed to the proapoptotic domain causing collateral apoptosis in renal proximal tubular epithelial cells during kidney filtration and excretion of the peptide.
What to Expect
Initial treatment phase. Based on primate data, measurable changes in body composition may begin. Renal markers (creatinine, BUN) should be monitored closely from the outset. Early signs of kidney stress may appear even at low doses.
Fat reduction becomes detectable via imaging in animal models. Primate studies showed progressive weight loss during this window. Renal tubular changes may begin to appear on urinalysis. Continued monitoring is essential.
Significant fat loss is observed in animal models. In obese monkeys, this period corresponded to the steepest weight loss trajectory. Kidney injury markers may become elevated; dose reduction or discontinuation should be considered if creatinine rises above baseline.
End of the standard 28-day treatment cycle. Primate data showed 7-15% total body weight loss and up to 38% reduction in body fat by this point. Treatment should be discontinued at day 28. Renal function monitoring should continue for at least 4-6 weeks after cessation.
Washout and recovery phase. Some weight regain is expected as adipose vasculature regenerates over time. Renal lesions observed in primate studies were reported as reversible during washout. Do not restart treatment until all renal markers have normalized.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 0.5mg | Daily |
| Moderate | 1mg | Daily |
| Aggressive | 2mg | Daily |
Note: WARNING: Clinical development permanently discontinued due to nephrotoxicity. Phase 1 human trial terminated early. Subcutaneous injection. Primate studies used 28-day treatment cycles at 0.43 mg/kg daily. This compound carries a high safety burden and should only be considered in a supervised research context with renal monitoring. The therapeutic window between fat-reducing and kidney-damaging doses is extremely narrow.
How to Inject Adipotide (FTPP)
Reconstitute lyophilized powder with bacteriostatic water (2 mL per 5 mg vial). Inject subcutaneously, rotating injection sites (abdomen, thigh). In primate research, the optimal dose was 0.43 mg/kg administered daily for 28 days. Human trial dosing started at 0.03 mg/kg daily. Given the terminated clinical program and established nephrotoxicity, there is no validated safe human dose. Any research use should begin at the lowest feasible dose with renal monitoring before, during, and after treatment. Do not exceed 28 consecutive days of administration.
Cycling Protocol
All published research used 28-day (4-week) treatment cycles. Extended use beyond 28 days has not been studied and is strongly discouraged given the cumulative nephrotoxic risk. Prolonged washout periods of at least 8 weeks are recommended to allow full renal recovery. Kidney function should be assessed before, during, and after any treatment cycle.
Pharmacokinetics
Source: Estimated from peptide pharmacokinetics; no published human PK data available. Short peptide with D-amino acid stabilization may extend half-life modestly.
Loading the interactive decay curve.
Side Effects
Nephrotoxicity is the primary and dose-limiting adverse effect. In primate studies, dose-dependent renal lesions were observed in all treated animals, ranging from minimal in low-dose groups to moderate in high-dose groups. Kidney injury manifested as altered renal tubular function, elevated creatinine, and evidence of tubular damage on histopathology. While these effects were characterized as reversible in primates, human trials revealed an unacceptably narrow therapeutic window. Additional observed side effects include transient dehydration, mild proteinuria, and injection site reactions. This compound should be considered high-risk from a safety standpoint, and any research use should include frequent renal function monitoring (BUN, creatinine, urinalysis).
Contraindications
- Any pre-existing kidney disease or impaired renal function
- History of nephrotoxic drug reactions
- Concurrent use of other nephrotoxic agents (NSAIDs, aminoglycosides, contrast dyes)
- Pregnancy or breastfeeding
- Dehydration or conditions predisposing to renal hypoperfusion
- Known hypersensitivity to any component of the peptide
- Hepatic impairment that may alter peptide clearance
- Cardiovascular disease or conditions affecting vascular integrity
- Children or adolescents (no pediatric safety data exists)
Drug Interactions
- NSAIDs (ibuprofen, naproxen) — additive nephrotoxic risk; avoid concurrent use
- Aminoglycoside antibiotics (gentamicin, tobramycin) — synergistic kidney toxicity
- ACE inhibitors and ARBs — may compound renal hemodynamic effects
- Metformin — increased risk of lactic acidosis if renal function is compromised by adipotide
- Iodinated contrast agents — compounded nephrotoxicity risk; separate by at least 2 weeks
- Diuretics — may worsen dehydration and increase renal concentration of the peptide
- Cyclosporine and tacrolimus — combined nephrotoxic burden is unacceptable
Storage & Stability
Molecular Profile
Related Peptides
References
- Reversal of obesity by targeted ablation of adipose tissue (Nature Medicine 2004)PubMed 15133506
- A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys (Sci Transl Med 2011)PubMed 22072637
- Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight (Am J Physiol 2009)PubMed
- Comment on "A peptidomimetic targeting white fat causes weight loss" (Sci Transl Med 2012)PubMed 22539771
- A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication (J Control Release 2013)PubMed 23871959