Adipotide

Origin and structure

Adipotide grew out of work by Renata Pasqualini and Wadih Arap at the University of Texas MD Anderson Cancer Center. Using in vivo phage display, their group screened for short peptides that home to particular blood vessels, and in a 2004 Nature Medicine paper they reported a cyclic motif, CKGGRAKDC, that binds the membrane protein prohibitin on the vessels of white fat. They chemically fused this fat-homing motif to D(KLAKLAK)2, a mirror-image (D-amino acid) proapoptotic sequence that disrupts mitochondrial membranes once a cell takes it up. The finished molecule, CKGGRAKDC-GG-D(KLAKLAK)2, was later named adipotide.

Chemically it is a peptidomimetic of 25 amino-acid residues with the molecular formula C111H206N36O28S2 and a molar mass of about 2,557 g/mol (PubChem CID 163360068, CAS 859216-15-2). It is not a natural hormone and has no counterpart in the body: it is a designed drug candidate. In its clinical paperwork it also went by prohibitin-targeting peptide 1 (prohibitin-TP01).

How it is thought to work

White fat, like any growing tissue, depends on its own blood supply. Adipotide works in two steps. The CKGGRAKDC half acts as a postcode: it binds prohibitin, which sits on the surface of the endothelial cells lining the vessels of white fat, and the cell pulls the whole molecule inside. Once internalised, the D(KLAKLAK)2 half breaks down the mitochondrial membranes, which triggers apoptosis, a controlled form of cell death. Killing the vessel cells cuts off the blood supply to fat, and the fat tissue is reabsorbed.

In animals this led to rapid loss of white fat and, with it, weight. Treated animals also ate less; studies in mice and rats suggested that destroying fat vasculature sends a signal to the brain that curbs food intake, independent of leptin, although the exact signal is unknown. Lean monkeys given the same dose did not lose weight, which the researchers read as a sign that the effect may be specific to obesity. The targeting is not perfect, though: in monkeys the kidney, which clears the molecule, was where the side effects appeared.

Is adipotide approved?

No. Adipotide has never been approved as a medicine by the EMA, in the Netherlands, by the FDA or anywhere else. It is an investigational compound whose only human trial was terminated without results.

In December 2010 MD Anderson granted an exclusive worldwide licence to the technology to Arrowhead (then Arrowhead Research, now Arrowhead Pharmaceuticals), which developed it through Ablaris Therapeutics, a majority-owned subsidiary. Arrowhead's annual reports describe a single phase 1 trial that began enrolling in 2012 under an FDA Investigational New Drug application, funded and managed by MD Anderson; by 2014 the company said it was spending no internal resources on the programme and was watching it only as a possible licensing candidate. From its 2015 annual report onwards Arrowhead mentioned adipotide only among its patents and licences, no longer as a development programme.

Research-grade adipotide, the lyophilised peptide sold for laboratory use, is not a medicine. It has no marketing authorisation, is not made under a medicines licence and may not be used in people. In the Netherlands it is not a registered medicine and does not appear in the CBG Geneesmiddeleninformatiebank.

What the research shows

The evidence for adipotide is almost entirely preclinical. The headline results:

• Mice and rats (Nature Medicine 2004; Diabetes 2010, 2012): aiming the proapoptotic peptide at fat vasculature reversed diet-induced obesity. In obese mice the original compound cut body weight by about 30% over four weeks; in later mouse and rat work it lowered food intake without signs of illness and improved glucose tolerance within days, independently of weight loss.
• Obese rhesus monkeys, dose-finding (Science Translational Medicine 2011): two monkeys received daily subcutaneous adipotide at rising doses for nine weeks and lost 15.4% and 20.4% of body weight; two saline controls did not change.
• Obese rhesus monkeys, fixed dose (same paper): 10 monkeys received 0.43 mg/kg daily for 28 days and 5 received saline. At the end of dosing the treated animals had lost 7.4% to 14.7% of body weight (controls +1.0% to −3.5%), and weight kept falling for about three weeks after dosing stopped. By the end of the four-week recovery period DEXA body fat was down 38.7% against 14.8% in controls (measured in 6 treated and 3 control animals), and the insulin response to a glucose load had fallen by 36.2% relative to controls, a sign of better insulin sensitivity.
• Other monkey data: an uncontrolled pilot in two obese baboons gave similar weight loss over 12 weeks, and single doses about 133 times the effective dose in obese rhesus monkeys were not lethal in monkeys.
• First-in-man phase 1 (NCT01262664, MD Anderson): a dose-escalation trial in obese men (BMI over 30) with metastatic or otherwise incurable prostate cancer, giving adipotide under the skin once daily for 28 days. It opened in May 2012 and was designed for up to 39 patients, but enrolled only 4, was terminated at the investigator's request (record closed January 2019) and posted no results.

Side effects and warnings

The clearest safety signal comes from the monkey studies, where the main side effect was kidney injury. At doses above 0.25 mg/kg, serum creatinine rose slightly to moderately in a dose-dependent way; treated animals produced more urine, with glucose and protein in the urine, and mild dehydration at the highest doses. A formal safety study in 20 lean monkeys (15 on adipotide) found minimal-to-moderate, dose-dependent damage to the kidney tubules, of which only minimal changes remained after a four-week recovery. The authors pointed out that renal D-amino acid oxidase is the only known mammalian enzyme that can break down the D(KLAKLAK)2 part of adipotide, which may make the kidney the main site where the molecule is processed. Blood lipids stayed normal and no fatty liver was seen.

A related MD Anderson drug built on the same D(KLAKLAK)2 cell-killing sequence, BMTP-11, reached its own first-in-man trial in prostate cancer, where the dose-limiting toxicity was reversible kidney damage with protein and casts in the urine and a rise in creatinine. That matches the animal picture for adipotide and is why the kidney is the organ of concern.

For adipotide itself there are no published human safety data: the single phase 1 trial enrolled only four patients and reported nothing. Any statement about how adipotide behaves in people is therefore an extrapolation from animals, not a finding from a human study.

Is adipotide banned in sport?

Adipotide is not named on the WADA Prohibited List, but that does not make it allowed. Class S0 (non-approved substances) bans, at all times, any pharmacological substance that is not covered by another class and that no government health authority has approved for human therapeutic use, with drugs in preclinical or clinical development and drugs whose development has stopped given as examples. Adipotide fits that description, so it is prohibited in and out of competition. The Dutch Dopingautoriteit publishes a Dutch translation of the same list.

Frequently asked questions

Is adipotide approved for weight loss?

No. Adipotide has never been approved as a medicine anywhere, for weight loss or anything else. The weight-loss results come from obese mice, rats and monkeys. The only human trial was a small phase 1 in prostate cancer that enrolled four patients and was terminated without results, and no further development has been reported since.

Why did adipotide target prostate cancer in its one human trial?

Because fat tissue produces substances that can promote prostate-cancer growth, the first-in-man trial tested whether shrinking fat with adipotide was safe in obese men with advanced prostate cancer. It was a safety (phase 1) study, not a weight-loss study, and it was terminated after enrolling only four of up to 39 planned patients, without posting results.

What is the main safety concern with adipotide?

The kidneys. In monkeys adipotide caused dose-dependent injury to the kidney tubules, with a rise in creatinine, extra urine, and glucose and protein in the urine, largely reversible after stopping. The researchers noted that the kidney holds the only known mammalian enzyme able to break down the D(KLAKLAK)2 part of the molecule. A related peptide, BMTP-11, had reversible kidney damage as its dose-limiting toxicity in people.

Is adipotide legal in the Netherlands?

It is not a registered medicine in the Netherlands and does not appear in the CBG Geneesmiddeleninformatiebank, so it cannot be prescribed or sold as a medicine. It is offered only as a research chemical for laboratory use, not for use in people. In sport it is prohibited at all times under WADA class S0.

Is adipotide the same as a GLP-1 drug like semaglutide?

No, and the mechanism is completely different. GLP-1 drugs act on receptors in the pancreas and brain to lower blood sugar and appetite, and they are approved medicines. Adipotide destroys the blood vessels that feed fat tissue, is approved nowhere, and has only been tested in animals plus one terminated phase 1 trial that reported nothing.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.