Adipotide: experimental fat-tissue-destroying weight-loss peptide (FTPP)
An experimental peptide that kills the blood vessels feeding fat tissue, causing dramatic fat loss in animal studies; development was abandoned due to kidney toxicity and it has never been tested in humans.
- Class
- Proapoptotic chimeric peptide / adipose vasculature-targeting peptidomimetic
- Status
- No approved therapeutic status. Development discontinued at preclinical stage. No human trials initiated in over a decade since primate data published.
- Best-supported effect
- Dramatic white adipose tissue reduction and insulin sensitivity improvement in obese non-human primate models (animal evidence only; no human translation established)
- Main caveat
- Clinical development abandoned due to dose-dependent kidney toxicity mechanistically intrinsic to the molecule. No human efficacy or safety data exist.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Proapoptotic chimeric peptide / adipose vasculature-targeting peptidomimetic
Evidence tier: Animal-only evidence
Status: No approved therapeutic status. Development discontinued at preclinical stage. No human trials initiated.
Best-supported effect: Dramatic white adipose tissue reduction and insulin sensitivity improvement in obese non-human primate models (animal evidence only; no human translation established)
Main caveat: Clinical development was abandoned due to dose-dependent kidney toxicity that is mechanistically intrinsic to the molecule. No human efficacy or safety data exist.
What this is
Adipotide (also known as FTPP, or Fat-Targeted Proapoptotic Peptide) is a synthetic chimeric peptidomimetic composed of two functional domains joined in a single molecule. The N-terminal cyclic motif CKGGRAKDC was identified from in vivo phage-display screens and selectively binds prohibitin expressed on endothelial cells in white adipose tissue vasculature. The C-terminal domain D(KLAKLAK)₂ is a synthetic sequence composed entirely of D-amino acids — conferring protease resistance — that disrupts mitochondrial membranes upon receptor-mediated internalization.
Rather than targeting fat cells directly, adipotide destroys the blood vessel network supplying white adipose tissue, causing adipocytes to die secondarily from ischemia. The molecule was developed at the University of Texas MD Anderson Cancer Center by Wadih Arap and Renata Pasqualini, building on their discovery that prohibitin is selectively expressed on adipose tissue vasculature. It produced striking fat-loss results in primate studies but was discontinued from clinical development when the same prohibitin receptor — expressed also in renal proximal tubular cells — produced dose-dependent, off-target kidney injury at the doses required for fat-loss efficacy.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None | No human trials have been conducted. Development was discontinued at the preclinical stage. |
| Animal | Moderate — single study, NHP | Dramatic body fat reduction, body weight loss, and insulin sensitivity improvement in obese rhesus macaques, baboons, and cynomolgus monkeys; accompanied by dose-dependent renal tubular injury at therapeutic doses |
| In vitro | None identified | No dedicated in vitro assay data are identifieds available literature |
| Computational | None identified | No structural prediction or docking data are identifieds available literature |
| Mechanism | Strong | Prohibitin-binding, endothelial cell internalization, mitochondrial membrane disruption, and subsequent adipose ischemia are well-characterized; the off-target kidney toxicity mechanism (prohibitin expression in renal tubular cells) is also mechanistically understood |
Evidence concentration note: The entire primate efficacy and safety evidence base rests on a single published study (Sci Transl Med, 2011). The evidence is internally compelling but has not been independently replicated in additional primate or animal programs.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Destroys white adipose tissue vasculature, producing rapid fat loss | Supported (animal) | Animal — single NHP study | Medium — single study, no human data |
| Produces meaningful body weight and body fat reduction in obese non-human primates | Supported (animal) | Animal — single NHP study | Medium — 38.7% body fat, 11% body weight reduction at 0.43 mg/kg/day over 28 days in obese rhesus macaques |
| Improves insulin sensitivity in obese non-human primates | Supported (animal) | Animal — single NHP study | Medium — 48.5% improvement in insulinogenic index in the same primate study |
| Kidney toxicity is a dose-dependent, mechanistically intrinsic safety liability | Supported (animal) | Animal — single NHP study | High — dose-dependent renal proximal tubular injury observed at therapeutic doses; mechanism (prohibitin in renal tubules) is intrinsic |
| Human fat-loss or weight-loss efficacy | Not established | None | High — no human trials have ever been conducted |
| "Reversible kidney injury means it is safe to self-administer" | Contradicted | Animal | High — primate reversibility was observed under controlled laboratory monitoring; the available literature explicitly states no monitoring infrastructure exists for real-world use, and reversibility cannot be assumed at higher doses, longer exposures, or in people with reduced renal reserve |
Experimental exposure
This section reports exposure used in animal experiments. It does not establish human dosing. No human dose exists for adipotide.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Animal experiment | Obese rhesus macaques (n=39), baboons (n=2), cynomolgus monkeys (n=52) | 0.43 mg/kg/day subcutaneous injection | 28 days | Body weight, body fat (DEXA/MRI), insulin AUC, renal biomarkers | Single published primate study; no human translation; dose-dependent renal tubular injury observed at the efficacious dose; no safe human dose established |
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| Dose-dependent renal proximal tubular degeneration and single-cell necrosis | Obese rhesus macaques at 0.43 mg/kg/day | Caused by prohibitin expression in renal proximal tubular cells — same receptor used for adipose targeting; intrinsic to the molecule's design |
| Elevated serum creatinine, glucosuria, proteinuria, increased epithelial cells in urine | Non-human primates at therapeutic doses | Renal injury markers concurrent with the fat-loss therapeutic effect; narrow therapeutic window between fat loss and nephrotoxicity |
| Reversibility of renal injury within 28 days of stopping in primates | Non-human primates, controlled conditions | Reversibility was demonstrated under continuous laboratory monitoring; available literature explicitly flags that this does not imply safe self-administration under real-world conditions |
| Long-term renal effects | Not established | No chronic exposure data; no human data; recovery from repeated-cycle exposures not characterized |
| Theoretical interaction with nephrotoxic agents | Mechanistic concern, no controlled data | available literature describes theoretical additive renal injury risk with NSAIDs, aminoglycosides, IV contrast agents, and chemotherapy regimens; no controlled interaction data available because no human exposure has occurred |
Long-term unknowns:
- Long-term adipose tissue regeneration and metabolic recovery after vasculature destruction are not characterized
- Effects of repeated or prolonged exposures on renal function are not established
- No human adverse-event data from regulated exposure exist; anecdotal reports from grey-market use are unverified
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved; no IND status | Clinical development discontinued following primate toxicity data; no active clinical trial program; material sold in research-chemical channels is not authorized for human use |
| International | Not approved in any jurisdiction | Per available sources, no regulatory authority has approved adipotide or has an active clinical trial program; the molecule is uniformly investigational-discontinued worldwide |
| WADA | Prohibited (per available sources, S0) | Per available sources, adipotide falls under WADA S0 — substances not approved by any government regulatory health authority for human therapeutic use; current list status not independently refreshed in this card |
Mechanism
Adipotide is a chimeric peptide designed around two distinct functional domains. The N-terminal cyclic motif CKGGRAKDC, identified through in vivo phage-display screening, binds specifically to prohibitin expressed on the luminal surface of endothelial cells in white adipose tissue vasculature. Following receptor-mediated internalization, the C-terminal D(KLAKLAK)₂ domain — composed entirely of D-amino acids for protease resistance — disrupts mitochondrial membranes, triggering endothelial cell apoptosis. The resulting destruction of the blood vessel network supplying white adipose tissue causes adipocytes to die secondarily from ischemia and nutrient deprivation, followed by resorption.
The kidney toxicity arises from the same prohibitin receptor expressed on renal proximal tubular cells. The targeting motif does not discriminate between adipose endothelium and renal tubular epithelium, resulting in off-target tubular degeneration and necrosis at therapeutic doses. This mechanism is intrinsic to the molecule's design — not a formulation artifact or dosing error — and constitutes the primary reason clinical development was discontinued.
The mechanism supporting fat loss is described as well-characterized in the available literature, verified through DEXA and MRI imaging of white adipose tissue volume changes in non-human primates.
Chemistry
| Field | Value |
|---|---|
| Full peptide | Chimeric: cyclic targeting motif CKGGRAKDC fused to peptidomimetic D(KLAKLAK)₂ |
| Targeting domain | CKGGRAKDC (cyclic; identified by in vivo phage display) |
| Apoptotic domain | D(KLAKLAK)₂ (D-amino acid sequence; protease-resistant) |
| Topology | Chimeric / conjugated |
| Modification | C-terminal domain composed of D-amino acids for protease resistance; N-terminal domain is cyclic |
| Origin type | Synthetic chimeric peptidomimetic |
| Sequence confidence | Needs review — detailed residue-level sequence and exact linkage chemistry are not individually extracted in the available literature |
Open questions
- Human translation: No human trial has ever been conducted. Whether the dramatic primate fat-loss results would translate to humans at any dose is entirely unknown.
- Therapeutic window in alternative species or dosing regimens: Whether intermittent dosing, lower doses, or alternate routes could produce fat loss while avoiding renal tubular injury has not been formally explored; clinical discontinuation means this is unlikely to be investigated in the current molecule's form.
- Modified targeting motifs: Whether next-generation variants could retain prohibitin binding selectivity for adipose vasculature while sparing renal tubular endothelium has not been published as a successor program.
- Long-term adipose regeneration: Effects on white adipose tissue revascularization and metabolic recovery after vasculature destruction are not well characterized; the mechanism predicts gradual revascularization over months but long-term data are absent.
- Brown vs white adipose tissue selectivity: The differential effect of adipotide on brown adipose tissue (which does not strongly express the same prohibitin pattern) versus white adipose tissue has not been formally distinguished in vivo.
- Real-world grey-market safety: Anecdotal reports from grey-market human use exist, but are unverified and not systematically collected; they are dominated by acute kidney injury case reports consistent with the primate toxicology profile but cannot be used as a basis for safety claims.
- Durability of fat loss: Long-term fat-loss durability beyond 28-day post-treatment follow-up in primates was not assessed.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.5283214449882507 | openfold3-mlx |
| ranking score | 0.6748614311218262 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.606 | global PDE — lower = better |
| disorder | 0.185 | fraction disordered |
| chain pair ipTM (A, B) | 0.528 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 97s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10949,
sequence = {CKGGRAKDCGGGDKLAKLAKDKLAKLAKLAK},
target = {anticancer},
author = {peptidemodel},
year = {2026},
status = {computed}
}