F tier · safety concern
The primate study that made adipotide famous reported, in the same abstract as the weight loss, that monkeys of three different species showed changes in renal proximal tubule function; the only human trial ever registered (NCT01262664) was terminated with 4 participants enrolled against a planned 15 and has never posted results. A documented target-organ toxicity plus an abandoned first-in-human trial with no published outcome is the bottom of the scale.
adipotide
Adipotide is a synthetic chimeric peptidomimetic developed at MD Anderson that links a nine-residue motif homing to prohibitin on white adipose tissue vasculature to a D-amino-acid amphipathic sequence that disrupts mitochondrial membranes. In obese rhesus monkeys it produced rapid weight loss and improved insulin sensitivity, and in the same experiments monkeys of three species showed changes in renal proximal tubule function. A first-in-human phase 1 trial in men with metastatic prostate cancer and obesity began in 2012 but was terminated with four patients enrolled and no results have ever been reported.
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available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
Adipotide is a lab-made peptide designed to find the blood vessels that feed fat tissue and kill them, so the fat starves. Obese monkeys given it lost about 11% of their body weight in four weeks, but their kidneys were also affected. A human trial started in 2012, enrolled only four patients, was stopped, and never reported any results.
regulatory status
Never approved; first-in-human trial terminated with 4 patients
Adipotide has never been approved by the FDA, EMA or MHRA and is not a licensed medicinal product in the UK; material sold under this name or as FTPP is an unlicensed research chemical and lawful supply is for laboratory use only, not human use. Arrowhead announced FDA clearance to initiate a phase 1 trial (NCT01262664, sponsored by MD Anderson Cancer Center, first patient dosed 11 July 2012) in men with metastatic prostate cancer and obesity; the registry records the trial as Terminated, actual enrolment 4 against a planned 15, reason 'Terminated per PI's request', with no results posted, and no further clinical development has been announced. Adipotide is not named on the WADA Prohibited List but falls within class S0 (Non-Approved Substances) as a substance with no current approval by any governmental regulatory health authority for human therapeutic use, prohibited at all times. It is not a lawful dietary-supplement ingredient in the UK or anywhere else.
how it works · proposed mechanism
Adipotide is not a metabolic drug in the conventional sense; it is a targeted cytotoxic. One end recognises prohibitin displayed on the vasculature of white adipose tissue, and the other end is a membrane-disrupting sequence built from D-amino acids so that it resists proteolysis and is inactive until it reaches a mitochondrial membrane. Fat loss is a consequence of destroying the blood supply to fat, not of altering appetite or nutrient partitioning.
Vascular homing to prohibitin
The CKGGRAKDC motif was selected by in vivo phage display to bind prohibitin on white adipose tissue endothelium, giving the construct its depot selectivity. Earlier mouse work using the same targeting principle reversed obesity by ablating adipose tissue. Everything about the compound's safety margin depends on how exclusive that homing actually is.
A generic mitochondrial toxin on the business end
D(KLAKLAK)2 is an amphipathic, protease-resistant helix that disrupts mitochondrial membranes and triggers apoptosis once internalised. It has no selectivity of its own; it is a warhead. Any tissue that takes up the construct will be damaged, which is why off-target uptake matters far more here than for a receptor-mediated peptide.
The kidney is where selectivity leaks
The Science Translational Medicine abstract states that at experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Proximal tubule cells reabsorb filtered peptides avidly, so this is a mechanistically expected consequence of circulating a small cationic cytotoxic peptide. Reversible in a closely monitored primate experiment is not the same as safe in unmonitored human use.
Weight loss is destructive and its durability is unclear
In the monkey study weight loss and metabolic improvement were substantial — roughly 11% of body weight over four weeks, a 27% fall in abdominal fat, and about half the previous insulin requirement. Effects persisted for around three weeks after treatment stopped and then began to reverse. Because the mechanism is ablation of adipose vasculature rather than regulation of energy balance, nothing in the design addresses why the animal was obese.
what’s reported
evidence shape
7 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The renal finding is not a footnote someone dug out of a supplementary table — it is in the published abstract, in the same sentence as the efficacy: monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function at the experimentally determined optimal doses. That is a target-organ toxicity in the exact tissue that filters and reabsorbs small cationic peptides, discovered in the study that is used to sell the compound. The human trial that would have defined whether any usable window exists (NCT01262664) enrolled 4 patients against a planned 15, was terminated at the investigator's request, and has never posted results in the seven years since its listed completion date. So the strongest human evidence for adipotide is an abandoned trial with no published outcome, and the strongest animal evidence comes packaged with kidney injury.
key published findings
- The Science Translational Medicine primate study reported targeted apoptosis within blood vessels of white adipose tissue, rapid weight loss and improved insulin resistance, and stated that at experimentally determined optimal doses monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function (Barnhart, 2011).
- Treated obese rhesus monkeys lost a mean 11% of body weight over four weeks, abdominal fat fell by 27%, and insulin requirement fell by roughly 50%, with weight loss persisting about three weeks after treatment ended before reversing.
- The only registered human trial, NCT01262664 (MD Anderson Cancer Center, phase 1, first-in-man, metastatic prostate cancer with obesity), started 24 May 2012 and is recorded as Terminated with actual enrolment of 4 against a planned 15, reason 'Terminated per PI's request'.
- No results have been posted to ClinicalTrials.gov for NCT01262664 and no peer-reviewed report of the trial has appeared, despite a listed primary completion date of 2 January 2019.
- Arrowhead announced FDA clearance and dosing of the first patient on 11 July 2012, in a trial whose stated primary objective was to identify a maximum tolerated dose — an objective for which no answer has ever been published.
- The targeting concept was first demonstrated in mice, where ligand-directed ablation of adipose tissue vasculature reversed obesity (Kolonin, Nature Medicine 2004).
limitations of the evidence
- Zero published human efficacy or safety outcomes exist; the single trial stopped at 4 patients and reported nothing.
- The renal finding was described as reversible under intensive laboratory monitoring in a short primate experiment, a setting that bears no resemblance to unsupervised use.
- No human pharmacokinetics, no maximum tolerated dose and no exposure-response relationship have ever been established.
- The cytotoxic module has no intrinsic selectivity, so any deviation in biodistribution translates directly into tissue damage rather than loss of efficacy.
- Weight loss is achieved by destroying adipose vasculature, and the long-term consequences for adipose tissue function, ectopic fat and metabolic health after depot ablation are unstudied.
- Nothing is known about repeat-cycle use, and the monkey data showed effects reversing within weeks of stopping.
documented safety signals
- Renal proximal tubule dysfunction in obese monkeys of three different species at optimal doses — a documented, dose-dependent target-organ toxicity reported in the primary publication's own abstract.
- The D(KLAKLAK)2 warhead is a nonselective mitochondrial membrane disruptor, so off-target uptake produces cell death rather than mere inefficacy.
- The first-in-human trial was terminated at the investigator's request after 4 of 15 planned patients with no published explanation, which leaves the human tolerability question entirely open rather than answered reassuringly.
- Unlicensed material sold as adipotide or FTPP has no verified identity, purity, D-amino-acid content or endotoxin specification, and the active form requires correct disulfide cyclisation of the homing motif.
identity
| full name | Adipotide, the prohibitin-targeting proapoptotic peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 |
| category | Metabolic |
| modality | peptide |
| formula | C111H206N36O28S2 |
| molar mass | 2557.2 g/mol |
| cas | 859216-15-2 |
| sequence | CKGGRAKDC-GG-D(KLAKLAK)2 (25 residues; a disulfide-cyclised CKGGRAKDC prohibitin-homing motif joined by a Gly-Gly linker to a tandem D-amino-acid amphipathic KLAKLAK mitochondria-disrupting module; the formula and mass recorded below are PubChem's, which correspond to the reduced, non-cyclised form and differ from the cyclised peptide by two hydrogens) |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C and protected from light. Once reconstituted, laboratory practice is refrigeration at 2-8 °C for short-term use, or aliquoting and freezing to avoid repeated freeze-thaw cycles. Handling information only; this material has no approved human use. |
| solubility | Short hydrophilic peptide, readily soluble in sterile or bacteriostatic water and in dilute aqueous buffer. Lot-specific solubility is stated on the certificate of analysis. |
| co-studied with | No human combination data exist. Because the compound's only documented target-organ toxicity is renal, any co-exposure to nephrotoxic or renally cleared agents would be the obvious concern in a laboratory design. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
7 citedClinicalTrials.gov, U.S. National Library of Medicine · 2019 · official
World Anti-Doping Agency · 2026 · official
Science Translational Medicine · 2011 · preclinical
Nature Medicine · 2004 · preclinical
PubChem, National Library of Medicine · 2026 · reference
Arrowhead Research Corporation · 2012 · press release
ScienceDaily · 2011 · press release
Sources marked tertiary or press release are the weakest citations on this page.
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