Adipotide

How does Adipotide work?

Adipotide is a two-part (chimeric) peptidomimetic. A homing domain (CKGGRAKDC) seeks out prohibitin, a protein that sits with annexin A2 on the endothelium — the inner lining — of the blood vessels that feed white adipose tissue. Once docked there, the peptide's second part, a proapoptotic payload written D(KLAKLAK)2, disrupts mitochondria and triggers apoptosis of that fat-feeding vasculature. Starved of its blood supply, the surrounding fat is resorbed. Every step of this mechanism has been demonstrated in animals only — none of it has been confirmed to occur in humans.

1. Adipose-vascular homing [1][3]. The CKGGRAKDC domain was identified by phage display as a sequence that homes to the vasculature of white adipose tissue, where it binds prohibitin — a protein presented, together with annexin A2, on the endothelium of fat-feeding blood vessels.
2. Proapoptotic payload [1]. Fused to the homing domain is D(KLAKLAK)2, a synthetic amphipathic peptide that is relatively inert outside cells but disrupts mitochondrial membranes once internalized, initiating programmed cell death (apoptosis).
3. Apoptosis of fat-feeding vasculature [1][2]. By concentrating the apoptotic payload on white-fat endothelium, adipotide triggers death of those vascular cells. This is a vascular-targeting strategy borrowed from tumor-vasculature work — the fat is not attacked directly.
4. Secondary adipocyte resorption [1][2]. With their local blood supply ablated, the adipocytes the vessels once fed are resorbed. In animal models this produced measurable loss of white adipose tissue and body weight.
5. Docking-target biology [3]. Follow-up work established that prohibitin and annexin A2 form a complex with the fatty-acid transporter CD36 on white-fat vascular endothelium, clarifying the molecular target adipotide relies on.
6. Species caveat. All of the above was demonstrated in mice and monkeys. There is no human data confirming that adipotide homes, ablates, or resorbs fat in people as it does in animals.

What is Adipotide used for?

Adipotide has been studied as an anti-obesity and, briefly, an oncology candidate — but its evidence base is almost entirely preclinical. Obese mice and obese monkeys lost fat and body weight on it, and the monkey study also showed improved insulin resistance. The one human trial ever opened was an oncology Phase 1 study that was terminated early and never reported. There is no demonstrated human efficacy or safety for any indication.

1. Obesity reversal in mice [1]. Kolonin and colleagues (2004) showed that the CKGGRAKDC-D(KLAKLAK)2 peptide ablated white adipose tissue and reversed obesity in obese mice — the foundational proof-of-concept for the whole approach.
2. Weight loss and insulin resistance in obese monkeys [2]. Barnhart and colleagues (2011) gave obese rhesus monkeys daily subcutaneous adipotide for 28 days; the animals lost roughly 11% of body weight and showed improved insulin sensitivity. Crucially, the same paper reported dose-dependent, reversible renal (kidney) changes as the dose-limiting toxicity.
3. Docking-target mechanism [3]. Salameh and colleagues (2016) established the prohibitin/annexin A2/CD36 complex on white-fat endothelium, grounding the biology adipotide exploits.
4. Human evidence — none demonstrated. The only human study, a first-in-human Phase 1 oncology trial (NCT01262664) at MD Anderson, was terminated early with 4 of 39 planned patients enrolled and no results published or posted. Adipotide has never shown efficacy or a characterized safety profile in humans.

How long does Adipotide take to work?

There is no human timeline for adipotide because there is no completed human study to derive one from. Any figure would be an extrapolation from animals, and animal-to-human timelines do not transfer reliably.

In the obese-monkey study, measurable weight loss (~11%) accumulated over a 28-day daily dosing cycle. That is an animal figure, not a human one. Because the single human trial was terminated before it produced data, no onset, no time-to-effect, and no duration-of-effect have been established in people. Treat any claimed human timeline as unsupported.

How is Adipotide dosed?

There is no validated human dose or protocol for adipotide. This is the single most important thing to understand about the compound. The only human-relevant figure that exists is the starting dose from the terminated Phase 1 trial — presented below strictly as an investigational reference point, not an endorsed protocol.

How is Adipotide administered?

In the animal studies and the terminated human trial, adipotide was given as a once-daily subcutaneous injection. Beyond the route itself, almost nothing about administration is established: no validated timing, no food rules, no characterized human half-life. The table below reflects that — most rows are honestly marked "not established."

What does Adipotide stack well with?

There are no studied human stacks for adipotide. Because its own human efficacy and safety are unestablished, combining it with anything is entirely unvalidated. It is sometimes discussed alongside metabolic and GLP-1 peptides, but that reflects a shared weight-loss theme, not a shared or synergistic mechanism.

1. No evidence-based stacks. No human study has evaluated adipotide in combination with any other compound. There is no basis to claim synergy with anything.
2. Mechanistically unrelated to metabolic peptides. Adipotide is often mentioned near GLP-1 and incretin agonists such as retatrutide, and metabolic compounds like MOTS-c, 5-Amino-1MQ, and AOD-9604. Those act on gut-hormone or metabolic pathways; adipotide ablates fat vasculature. The overlap is thematic, not mechanistic.
3. No invented synergy. Any protocol pairing adipotide with a metabolic peptide is speculative. Given adipotide's unresolved renal-safety signal and absent human data, stacking compounds its unknowns rather than reducing them.

What are the side effects of Adipotide?

The most important safety signal for adipotide comes from animals, not humans: in obese monkeys the dose-limiting toxicity was reversible kidney (renal) change. It was reversible in that model, but whether it is reversible — or even occurs the same way — in humans is unknown, because the single human trial was terminated before a safety profile could be established. Everything below should be read against that backdrop of unknown human safety.

Does Adipotide interact with other drugs?

There is no human drug-interaction data for adipotide. Any interaction concern is theoretical, inferred from its mechanism rather than observed in people.

1. No human interaction studies. No published research characterizes adipotide's interactions with any drug in humans.
2. Theoretical renal caution. Given the animal kidney signal, co-administration with nephrotoxic drugs would be a theoretical concern — but this has not been studied.
3. No established pharmacokinetic interactions. Because adipotide's human pharmacokinetics are uncharacterized, drug-drug PK interactions cannot be described.

How should Adipotide be stored?

1. Lyophilized (powder) form: Store at -20°C for long-term storage; refrigerate at 2–8°C for short-term.
2. Reconstituted solution: Store at 2–8°C; use within 28–30 days.
3. Reconstitute with bacteriostatic water for injection (BAC water). Swirl gently — do not shake.
4. Never freeze reconstituted solution.
5. Protect from light. Store in original carton.
6. Discard if cloudy, discolored, or contains particles.

What are the limitations of Adipotide research?

This is the most important section on the page. Adipotide has no proven human efficacy and no characterized human safety. The one human trial ever opened was halted early and never reported. A dose-limiting kidney-toxicity signal appeared in primates. Every positive result is from animals. Read the evidence accordingly.

Where to source Adipotide

Adipotide is not FDA-approved and is sold only as a research-grade peptide, by a limited number of research suppliers. In PP's vetted directory it is currently listed by Swiss Chems. As with any unvalidated research compound, published batch documentation and third-party testing matter more, not less.

Adipotide FAQ

References

1. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10(6):625-632. https://pubmed.ncbi.nlm.nih.gov/15133506/
2. Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011;3(108):108ra112. https://pubmed.ncbi.nlm.nih.gov/22072637/
3. Salameh A, Daquinag AC, Staquicini DI, et al. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016;1(10):e86351. https://pubmed.ncbi.nlm.nih.gov/27468426/

Published Studies