TL;DR
Rhesus monkeys lost 11% body fat in 4 weeks. Their kidneys paid the price.
What is it? A chimeric peptide: CKGGRAKDC (a homing sequence for white-fat vessel endothelium) fused to D(KLAKLAK)₂ (a mitochondria-rupturing pro-apoptotic peptide). Invented at MD Anderson in the early 2000s.
What does it do? CKGGRAKDC binds prohibitin on adipose-tissue vessel endothelium. (KLAKLAK)₂ then shreds mitochondrial membranes, apoptosing the endothelium and starving adipocytes of blood supply.
Does the evidence hold up? Obese mice (Kolonin, Nat Med 2004, PMID 15133506) and obese rhesus macaques (Barnhart, Sci Transl Med 2011, PMID 22072636) showed substantial fat loss plus dose-dependent renal tubular injury. One small Phase 1 did not advance.
Who uses it? Essentially only labs. Gray-market research-chemical vendors occasionally list it for fat-loss self-experimenters. That is a dangerous application given the primate renal signal.
Bottom line? A peptide that kills fat by killing the plumbing. Primate kidneys said no. Humans have not seen a Phase 2.
What It Is
Adipotide — also referred to as FTPP (Fat-Targeted Pro-apoptotic Peptide) or the prohibitin-targeted peptidomimetic — is a chimeric synthetic peptide designed to destroy white adipose tissue by killing the blood vessels that supply it. It was invented in 2004 in the laboratory of Renata Pasqualini and Wadih Arap at the University of Texas MD Anderson Cancer Center, with Mikhail Kolonin as first author. The approach translated a strategy that the same laboratory had developed for targeted tumor-vasculature ablation (fusing a tumor-vessel-homing peptide to a pro-apoptotic mitochondrial-disrupting peptide) into the adipose-tissue problem.
Structurally, Adipotide is a two-domain construct connected by a short linker: the N-terminal half is the homing peptide CKGGRAKDC (a disulfide-cyclized nonapeptide identified by in vivo phage display as a selective binder of white-fat vasculature); the C-terminal half is D(KLAKLAK)₂, a D-amino-acid amphipathic helical sequence that disrupts mitochondrial membranes once internalized into target cells. The two are joined by a short glycine-glycine linker. The overall molecule is therefore a ~30-amino-acid chimeric peptidomimetic, rather than a "natural" peptide.
The target of the homing sequence is prohibitin, a multifunctional mitochondrial and plasma-membrane protein. Prohibitin is expressed on the luminal surface of white adipose tissue microvasculature and functions as a vascular-bed-specific "zip code" for CKGGRAKDC-bearing peptides. Prohibitin expression is not confined to adipose vasculature — it is also expressed in mitochondria, in certain tumor vasculatures, and in the kidney, which turns out to be the key to the toxicity story.
Adipotide is not a metabolic fat-loss drug in the usual sense. It does not alter lipolysis, lipogenesis, appetite, nutrient partitioning, or energy expenditure at the adipocyte level. It kills a specific vascular bed. Adipocytes in that bed die from ischemia, and the surrounding fat pad involutes. Regrowth requires re-vascularization; in obese rodents and primates, the compound produces durable fat-mass loss over weeks after dosing ends. This makes Adipotide pharmacologically unusual and interesting — but the same property that produces its effect (targeted vascular apoptosis) is the property that limits it (prohibitin is also present outside adipose).
Mechanism of Action
- Vascular homing via prohibitin — The N-terminal CKGGRAKDC nonapeptide binds prohibitin expressed on the luminal endothelium of white adipose tissue microvasculature. Prohibitin was identified as the cognate receptor in the original 2004 Kolonin Nat Med paper via affinity chromatography and co-localization studies (Kolonin et al., Nat Med 2004; PMID 15133506). The binding is sufficiently tissue-selective that systemically administered CKGGRAKDC-fluorophore conjugates accumulate preferentially in adipose vascular beds.
- Pro-apoptotic mitochondrial disruption — The C-terminal D(KLAKLAK)₂ sequence is an amphipathic α-helical cationic peptide. Once internalized into the target endothelial cell, the helix inserts into the mitochondrial inner membrane, depolarizing it and releasing cytochrome c. The resulting caspase cascade drives endothelial apoptosis. The D-stereochemistry provides resistance to cytoplasmic proteases during transit.
- Endothelial apoptosis → vascular rarefaction — Loss of endothelial cells in the adipose microvasculature reduces blood flow to the tissue. Capillary density falls and the vascular "scaffold" that supports adipocyte viability collapses.
- Adipocyte ischemic death — Deprived of their blood supply, adipocytes undergo ischemic necrosis and adjacent phagocytic cleanup. Fat pad mass decreases over days to weeks.
- Durable body-composition change — Because adipocytes do not readily regenerate and the vascular scaffold must be rebuilt from remaining endothelial precursors, the body-composition change persists after compound washout. In primate studies, body fat did not recover to baseline during the 4-week follow-up after dosing ended.
- Prohibitin expression on renal tubular cells — the toxicity mechanism — Prohibitin is not adipose-exclusive. It is also expressed on renal tubular epithelial cells. Systemic Adipotide exposure delivers the pro-apoptotic C-terminal domain to the kidney, and at the dose range required for adipose-tissue effects it produces dose-dependent renal tubular injury / necrosis. This is the compound's dose-limiting toxicity.
- Possible off-target effects in tumor vasculature — Some tumor types express CKGGRAKDC-binding prohibitin, so Adipotide has been studied as an antitumor agent in prostate cancer models — a related but distinct therapeutic program.
- No effect on appetite, thermogenesis, or lipolysis — The mechanism is purely vascular-ablative. Food intake in dosed primates was unchanged; weight loss arose entirely from adipose tissue destruction.
What the Research Shows
- Original mouse obesity reversal (Kolonin 2004; PMID 15133506) — Obese ob/ob mice and diet-induced obese C57BL/6J mice received daily subcutaneous Adipotide. Body weight and fat mass decreased rapidly and durably; glucose tolerance and insulin sensitivity normalized. Authors reported normalization of metabolism "without detectable adverse effects" at the doses tested in mice, with the caveat that rodent renal handling differs from primate renal handling.
- Rhesus macaque obesity (Barnhart 2011; Sci Transl Med; PMID 22072636) — Spontaneously obese rhesus macaques received Adipotide daily for 28 days. Approximately 11% reduction in body fat in 4 weeks, with DEXA-confirmed fat-pad involution and improved insulin sensitivity. Food intake did not decline — the weight loss was adipose-specific. Critically, the primate study also documented dose-dependent renal tubular injury as the consistent toxicity, especially elevated BUN, creatinine, and urinary biomarkers of proximal tubule damage.
- Dose-ranging and toxicology refinements — Subsequent preclinical work explored dose-titration, formulation, and schedule modifications aimed at widening the therapeutic index. None of these substantially eliminated the renal toxicity at fat-loss-effective doses.
- Prostate cancer line of work — The same laboratory and others explored Adipotide and related prohibitin-targeted constructs in prostate cancer models (where some tumor vasculatures overexpress prohibitin). This is a separate therapeutic program from the obesity application.
- Limited clinical exploration — A 2013 Phase 1 dose-escalation study in obese men with prostate cancer was initiated (ClinicalTrials.gov NCT01813071, listed as Prohibitin-TP01 / Adipotide). Publicly available results and outcome data are limited; the compound did not progress to advanced clinical development in the obesity indication.
- Canine weight-loss exploration — Brief work in dogs as a model for veterinary weight management; did not mature into a veterinary product.
- No independent laboratory has produced a positive body-composition read-out without the parallel renal toxicity signal.
Critical Context — Why Adipotide Is Not a Clinical Drug
The reason Adipotide never progressed to a late-stage obesity development program is that the therapeutic window between fat-mass reduction and nephrotoxicity could not be engineered wide enough. Every major preclinical program documented both effects together. In a disease area — obesity — with GLP-1 / GLP-1+GIP / tri-agonist agents now offering 15–25% body-weight reduction at acceptable safety margins, a peptide that causes tubular kidney injury at fat-loss-effective doses is not a developable candidate. Community use of Adipotide sold through research-chemical channels for body-composition purposes sits outside any responsible safety frame.
Human Data
The published human clinical experience with Adipotide is extremely limited.
- Phase I dose-escalation in obese men with prostate cancer (NCT01813071) — Listed on ClinicalTrials.gov around 2013, sponsored by Arrowhead Research (Arrowhead Pharmaceuticals) / Ablaris Therapeutics at the time. Designed as dose-escalation primarily to characterize safety and the primary body-composition end-point in obese men with prostate cancer. Detailed results have not been fully published in the peer-reviewed literature, and the compound did not advance to a Phase II or Phase III obesity program.
- No dedicated non-oncology obesity trial published — Despite the striking rhesus macaque fat-loss data, no registered randomized placebo-controlled obesity trial in otherwise healthy obese adults has been published.
- Community self-administration — Adipotide has appeared intermittently in gray-market research-chemical listings aimed at fat-loss self-experimenters. Community reports are sparse, often conflate Adipotide with unrelated compounds, and in any responsible frame should be treated as cautionary anecdote rather than signal.
Dosing from the Literature
The doses below are reproduced from the published preclinical literature for historical / research reference. They are not a human use guide. No FDA-approved human dose exists, and the primate data document dose-dependent renal injury at every efficacy-positive dose tested.
| Species / Study | Dose | Route / Schedule | Notes |
|---|
| DIO mouse (Kolonin 2004) | 0.4–3 mg/kg | Daily SubQ × 2–4 weeks | Reference fat-loss dose in mice. Renal handling differs from primate. |
| ob/ob mouse (Kolonin 2004) | ~0.4–1 mg/kg | Daily SubQ × 2–4 weeks | Mass reduction with glucose-tolerance improvement. |
| Obese rhesus macaque (Barnhart 2011) | ~0.5 mg/kg | Daily SubQ × 28 days | ~11% body-fat reduction; concurrent renal tubular injury documented. |
| Human Phase I (NCT01813071) | Dose-escalation (undisclosed ranges) | Daily SubQ × 28 days | Obese men with prostate cancer. Results not fully published. |
| Community research-chemical use | Variable — 0.5–1 mg/kg cited | Daily SubQ | Extreme risk. No safety monitoring frame exists for community use. |
Dosing Disclaimer — Read This
The primate studies that document 11% body-fat reduction in 4 weeks also document dose-dependent renal tubular injury at those same doses. There is no published dose range in any species that produces the fat-loss phenotype without the parallel renal signal. Self-administration of Adipotide obtained through research-chemical channels, at community-cited doses, exposes the user to renal injury with zero clinical-grade safety monitoring. This is not a compound to experiment with.
Reconstitution & Storage
This section is provided for research-laboratory context. Nothing here should be read as an endorsement of human use.
- Typical supply form — Lyophilized powder in 5 mg or 10 mg vials. Research-chemical grade; identity and purity vary dramatically by source.
- Reconstitution — Sterile phosphate-buffered saline or bacteriostatic water. Slow addition to minimize denaturation of the amphipathic helix domain. Do not shake.
- Storage — Lyophilized powder at −20°C long-term. Reconstituted solution at 2–8°C; short-term use only.
- Identity / purity — The D(KLAKLAK)₂ pro-apoptotic domain requires specific D-amino-acid stereochemistry; mis-synthesis produces an inactive or differently active compound. HPLC + mass-spec confirmation is essential for research use.
- No clinical / calculator link — The Kalios dosing calculator does not currently support Adipotide because the compound is not recommended for human use.
Side Effects & Risks
Important
Adipotide caused dose-dependent renal tubular injury in primates. Gray-market vendors listing it for fat-loss self-experimentation are selling primate-toxic material. Bring this to your provider, and strongly reconsider.
- Renal tubular injury — the dose-limiting toxicity — Dose-dependent proximal tubule damage in all studied primate species. Elevated BUN / creatinine, urinary biomarkers of tubular injury (KIM-1, NGAL), and histologic tubular necrosis. This is not a theoretical risk — it is a consistent observed toxicity at every fat-loss-effective dose.
- Dehydration and electrolyte disturbance — Concurrent with renal injury. Can be clinically significant; requires monitoring and potential intervention.
- Off-target vascular damage — Prohibitin-expressing vascular beds outside adipose (including kidney and possibly other tissues) receive the pro-apoptotic payload. Theoretical and observed damage to non-target tissues.
- Irreversible, cosmetically disproportionate fat loss — Because adipocytes killed by vascular destruction do not reliably regenerate, fat loss is effectively permanent. Disproportionate depletion of specific fat pads could create long-lasting cosmetic deformity.
- Adipose hormone changes — Fat tissue is endocrine-active (leptin, adiponectin, estrogen conversion). Rapid adipose-tissue destruction could produce disordered leptin signaling and secondary metabolic consequences.
- No established safe dose in humans — Phase I data is limited and not fully published; no dose establishes a safety threshold for routine human use.
- Injection site reactions — Local inflammation reported.
- Pregnancy / lactation — Contraindicated.
- Drug interactions — Unstudied. Avoid concurrent nephrotoxic agents (NSAIDs, aminoglycosides, contrast) categorically.
- Purity / identity risk — Research-chemical vendors vary widely. A mis-synthesized Adipotide may be inactive or have altered specificity. Either failure mode is dangerous.
Bloodwork & Monitoring
- Baseline and frequent renal function — BUN, creatinine, eGFR, urinalysis with microscopy before and at regular intervals during any exposure. Urinary KIM-1 and NGAL are more sensitive tubular-injury biomarkers if available.
- Electrolytes — Sodium, potassium, magnesium, phosphate — renal injury disturbs all of these.
- Fluid status — Weight, blood pressure, orthostatic vitals, fluid intake / output tracking.
- Hepatic function — AST, ALT, bilirubin.
- Complete blood count — Baseline and periodic.
- Body composition — DEXA for objective fat-mass tracking if used.
- Fasting glucose and insulin — Metabolic effects track body-composition change.
- Symptom-directed workup — Any new back / flank pain, decreased urine output, peripheral edema, or malaise warrants immediate cessation and evaluation.
Commonly Stacked With
Not recommended in any stack
Adipotide's preclinical renal toxicity, lack of a validated human dose, and absence of a clinical safety framework make it unsuitable for combination with other compounds. Any claim of "safe stacking" rests on no evidence. The compounds that could be paired on mechanistic grounds (GLP-1 agonists, tesamorelin, stimulant fat-loss agents) would compound both the cosmetic risk of irreversible fat loss and the practical difficulty of separating drug-driven vs peptide-driven adverse events.
GLP-1 and GLP-1+GIP agonists are FDA-approved for chronic weight management with well-characterized safety databases, predictable body-composition effects in the 12–25% body-weight range, and reversible dose-dependent responses. These are the evidence-based choices for pharmacologic fat loss. Adipotide is not a reasonable substitute or adjunct.
→ Check compound compatibility in the Stack Builder
Regulatory Status
Current Status — April 2026
Adipotide is not FDA-approved for any indication. It has not progressed beyond a limited Phase I dose-escalation in obese men with prostate cancer (NCT01813071) and is not currently in active clinical development for obesity or any other indication.
Adipotide is not specifically listed on the FDA Bulk Drug Substances Category 1 or Category 2 peptide lists. It exists in a regulatory gray zone similar to other preclinical experimental peptidomimetics: available for research use but not legally available for human clinical use in any jurisdiction.
Adipotide is not specifically listed on the WADA Prohibited List 2026. A fat-vasculature-ablative peptide does not fit cleanly within any existing S-class (stimulants, anabolic agents, etc.), but an athletics federation could plausibly evaluate it under broad categories (S5 diuretics / masking; S0 non-approved substances) if an athlete were found using it.
Adipotide is not part of HHS Secretary Robert F. Kennedy Jr.'s February 2026 peptide-reclassification announcement. No realistic regulatory path to US clinical availability exists absent a sponsor pursuing late-stage development — which, given the renal toxicity history and the maturation of GLP-1-class obesity pharmacology, is not commercially plausible.
Cost & Access
Adipotide is not approved for human use in any jurisdiction. It is available only through research-chemical suppliers for laboratory research purposes.
US 503A / 503B compounding pharmacies do not compound Adipotide. It is not part of HHS Secretary Robert F. Kennedy Jr.'s February 2026 peptide-reclassification announcement. The compound's preclinical renal toxicity and lack of an active clinical development program mean that personal-use acquisition through research-chemical channels is the only practical "access" route — and that route exposes the user to all of the compound's documented risks with no clinical safety monitoring.
For people looking for pharmacologic body-composition assistance, the evidence-based choices are FDA-approved GLP-1 or GLP-1+GIP agonists (semaglutide, tirzepatide) prescribed through a licensed clinician.
Kalios does not sell compounds and does not recommend Adipotide for human use.
Related Compounds
People researching Adipotide often also look at these:
Modified GH fragment (AOD = anti-obesity drug) developed by Metabolic Pharmaceuticals for fat loss.
Triple monoamine reuptake inhibitor (5-HT, DA, NE). Non-GLP-1 weight-loss alternative.
NNMT inhibitor. Preserves NAD+ and methyl-donor pools while promoting adipose lipolysis in preclinical models.
Triple GLP-1 / GIP / glucagon agonist. The most potent obesity drug in Phase III, ~24% body weight reduction.
Key References
- 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. PMID: 15133506. (The original Adipotide paper — describes CKGGRAKDC homing, prohibitin receptor identification, and ob/ob + DIO mouse obesity reversal.)
- Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011;3(108):108ra112. PMID: 22072636. (Rhesus macaque obesity study documenting 11% body-fat reduction and dose-dependent renal tubular injury.)
- Reitman ML. Magic bullets melt fat. Nat Med. 2004;10(6):581-582. PMID: 15170200. (Editorial commentary accompanying the 2004 Kolonin Nat Med paper, framing promise and mechanism.)
- Arap W, Pasqualini R, Ruoslahti E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 1998;279(5349):377-380. PMID: 9430587. (The methodology paper for tumor-vasculature-homing peptide discovery that the Adipotide program translated to adipose.)
- Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Rio GD, Krajewski S, Lombardo CR, Rao R, Ruoslahti E, Bredesen DE, Pasqualini R. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999;5(9):1032-1038. PMID: 10470080. (The foundational paper describing the D(KLAKLAK)₂ pro-apoptotic mitochondrial-disrupting sequence that Adipotide reuses.)
- ClinicalTrials.gov. Safety Study of Adipotide (Prohibitin-TP01) in Obese Men With Prostate Cancer. NCT01813071. (Phase I dose-escalation; limited public outcome data.)
- Kolonin MG, Sergeeva A, Staquicini DI, Smith TL, Tarleton CA, Molldrem JJ, Marchiò S, Pasqualini R, Arap W. Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates Prostate Cancer Metastasis to Bone. Cancer Res. 2017;77(12):3144-3150. PMID: 28487385. (Related Kolonin / Arap / Pasqualini vascular-targeting program.)
- Daquinag AC, Tseng C, Salameh A, Zhang Y, Amaya-Manzanares F, Dadbin A, Florez F, Scherer PE, Kolonin MG. Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development. Cell Death Differ. 2015;22(2):351-363. PMID: 25342467. (Follow-up vascular-progenitor depletion work in adipose biology.)
- Kolonin MG, Pasqualini R, Arap W. Molecular addresses in blood vessels as targets for therapy. Curr Opin Chem Biol. 2001;5(3):308-313. PMID: 11479124. (Review framing the vascular-homing-peptide paradigm that underlies Adipotide.)
- Giordano RJ, Cardó-Vila M, Lahdenranta J, Pasqualini R, Arap W. Biopanning and rapid analysis of selective interactive ligands. Nat Med. 2001;7(11):1249-1253. PMID: 11689892. (Methodology for in vivo phage display, which identified CKGGRAKDC.)
- Hossen MN, Kajimoto K, Akita H, Hyodo M, Harashima H. Vascular-targeted nanotherapy for obesity: unexpected passive targeting mechanism to obese adipose for the enhancement of active drug delivery. J Control Release. 2012;163(1):101-110. PMID: 22989535. (Related adipose-vascular-targeting therapeutic literature.)
- Daquinag AC, Dadbin A, Snyder B, Wang X, Sahin AA, Ueno NT, Kolonin MG. Non-glycanated Decorin Is a Drug Target on Human Adipose Stromal Cells. Mol Ther Oncolytics. 2017;6:1-9. PMID: 28616465. (Subsequent Kolonin-group adipose-targeting work.)
Last updated: April 2026 | Profile authored by Kalios Peptides research team