Peptide profile
FTPP Adipotide
Targeted fat-depot elimination via vascular apoptosis · also known as Adipotide, CKGGRAKDC-GG-D(KLAKLAK)2, Prohibitin-targeting peptide
Compare FTPP Adipotide with other peptides →Summary
Adipotide is a pro-apoptotic peptidomimetic designed to selectively destroy the blood supply feeding white adipose tissue (WAT), causing fat cell death through targeted vascular disruption. It was developed at MD Anderson Cancer Center primarily as an anti-obesity compound and has shown dramatic fat loss in non-human primate studies. Human clinical data remains extremely limited, and it is considered a research compound only.
- Typical dose
- ~100–250 mcg/kg/day (based on non-human primate research; no validated human dose exists)
- Half-life
- ~1–2 hours (estimated based on peptide pharmacokinetics; not formally established in humans)
- Route
- Subcutaneous
- Cycle length
- 4–28 days (primate studies used cycles of 4–28 days; optimal human cycle unknown)
Mechanism
How it works
Adipotide consists of a targeting domain (CKGGRAKDC) that binds prohibitin, a protein selectively overexpressed on the luminal surface of blood vessels feeding white adipose tissue, fused via a GG linker to a pro-apoptotic domain (D(KLAKLAK)2) that disrupts mitochondrial membranes. Upon binding prohibitin on adipose vasculature endothelial cells, the apoptotic domain induces mitochondrial depolarization and cell death, collapsing the blood vessels that supply fat depots. The resulting ischemia causes programmed death of adipocytes and subsequent reduction in fat mass.
Reported in research
Benefits
- Significant reduction in white adipose tissue mass, particularly visceral fat
- Observed improvements in insulin sensitivity concurrent with fat loss in primate studies
- Potential reduction in BMI and body weight independent of caloric restriction alone
- Highly targeted mechanism with selectivity for adipose vasculature, sparing other tissues in animal models
Context, not a prescription
Dosing
- Typical range
- ~100–250 mcg/kg/day (based on non-human primate research; no validated human dose exists) (Subcutaneous)
- Cycle length
- 4–28 days (primate studies used cycles of 4–28 days; optimal human cycle unknown)
- Half-life
- ~1–2 hours (estimated based on peptide pharmacokinetics; not formally established in humans)
Safety
Side effects & contraindications
Possible side effects
- Nephrotoxicity (kidney damage) — the most serious observed adverse effect in primate studies
- Elevated creatinine and BUN indicative of acute kidney stress
- Injection site reactions including redness, swelling, and pain
- Transient dehydration due to rapid fat mobilization
- Fatigue and general malaise during treatment periods
- Potential hypotension from fluid shifts
Contraindications
- Pre-existing renal impairment or kidney disease
- Pregnancy or breastfeeding
- Individuals with compromised cardiovascular function
- Active malignancy or immunosuppressed individuals
- Concurrent use of nephrotoxic drugs (NSAIDs, certain antibiotics, contrast agents)
Research information, not medical advice. Always consult a licensed clinician before considering any peptide.
In depth
Full profile
What it does
Reduction in visible fat, particularly around the abdomen and waist; possible improvement in blood sugar levels; potential weight loss on the scale.
How it works
Think of your body's fat tissue like a neighborhood that depends on a network of water pipes. Adipotide is like a specialized crew that identifies only the pipes leading to the unwanted neighborhood, cuts them off, and causes that district to wither away — leaving the rest of the city (your healthy tissues) untouched.
After a subcutaneous injection, Adipotide circulates in the bloodstream and docks onto a protein called prohibitin, which is found almost exclusively on the walls of blood vessels inside fat tissue. Once attached, it triggers those cells to self-destruct, cutting off the fat depot's blood supply and causing fat cells to die.
What to expect
In primate studies, measurable fat loss was observed within the first 1–2 weeks of daily dosing. Humans have not been formally studied, so onset is unknown.
- Week 1: Peptide begins binding to adipose vasculature. Some users may notice slight injection site reactions. Kidney labs should be checked at baseline.
- Weeks 2-4: Fat reduction may become visible, especially in visceral/abdominal areas. Energy levels may fluctuate. Kidney markers should be monitored weekly.
- Weeks 4-8: In primate studies, significant body fat percentage reduction was maintained post-cycle. Long-term human outcomes are unknown. Post-cycle kidney recovery should be confirmed with labs.
Good to know
- Stay well-hydrated throughout the cycle — drink at least 2–3 liters of water daily
- Monitor kidney function (creatinine, BUN, eGFR) via blood tests before, during, and after any research protocol
- Start with the lowest possible dose and assess tolerance before escalating
Staying safe
- Kidney stress — the most important risk, showing up as changes in urine and lab values
- Injection site redness or swelling
- Fatigue and tiredness during the cycle
- Mild dehydration
Avoid if you have:
- Anyone with kidney problems or a history of kidney disease
- Pregnant or breastfeeding women
- People taking medications that are hard on the kidneys
Mechanism of action
Adipotide is a bimodal chimeric peptide consisting of a vascular-homing domain CKGGRAKDC that binds prohibitin (PHB) — a mitochondria-associated protein aberrantly translocated to the luminal surface of white adipose tissue endothelium — fused via a GG dipeptide linker to the pro-apoptotic sequence D(KLAKLAK)2. PHB surface expression on WAT vasculature provides tissue-specific targeting selectivity. Upon receptor-mediated endocytosis and internalization, the KLAKLAK domain disrupts mitochondrial membrane integrity via direct interaction with the inner mitochondrial membrane phospholipids, triggering cytochrome c release, caspase cascade activation, and ultimately apoptosis of the endothelial cells. This vascular ablation induces ischemic necrosis and apoptosis in dependent adipocytes, with consequent reduction in fat depot volume. Selectivity for WAT over brown adipose tissue (BAT) vasculature and other organ vasculature appears to stem from differential PHB cell-surface expression patterns.
Following subcutaneous injection, the peptide enters systemic circulation with rapid distribution. The CKGGRAKDC moiety demonstrates ligand-receptor binding affinity for PHB at the luminal endothelial surface of WAT-feeding vessels. Following internalization via endocytosis, the D(KLAKLAK)2 domain inserts into and disrupts mitochondrial membranes, triggering intrinsic apoptosis. Vascular collapse leads to downstream ischemic adipocyte death. Renal filtration of peptide fragments and metabolic byproducts is believed to be responsible for the observed nephrotoxic effects, possibly via tubular accumulation.
Pharmacodynamics
Pharmacodynamic effects on adipose vasculature likely begin within hours of the first dose based on peptide-receptor binding kinetics. Histological evidence of apoptotic endothelial cells was observed within 24–72 hours in murine models. Measurable fat mass reduction in rhesus macaques was observed at 4 weeks with daily dosing.
Reduction in fat depot volume (particularly visceral WAT), decreased plasma leptin, improved insulin sensitivity, reduced BMI — all documented in non-human primate studies. Concomitant rise in serum creatinine and BUN reflects renal stress that reversed upon discontinuation in study animals (at lower doses).
Timeline
- Days 1-3: Initial receptor engagement; PHB-binding of CKGGRAKDC domain on WAT endothelium; endothelial apoptosis begins; baseline kidney labs essential before initiation.
- Weeks 1-2: Progressive vascular collapse in WAT depots; adipocyte ischemia and apoptosis underway; measurable reduction in fat depot MRI volume reported in primate studies by day 14; creatinine elevation may begin — monitor closely.
- Weeks 2-8: Sustained reduction in WAT volume; improved insulin sensitivity and reduced leptin levels in primate studies; renal stress peaks and should stabilize or decline upon dose reduction; post-cycle labs confirm recovery of renal indices.
Comparisons
- FTPP Adipotide — effectiveness High, safety Caution, cost $$$, Medium to use
- AOD-9604 — effectiveness Moderate, safety Good, cost $$, Medium to use
- Tesamorelin — effectiveness Moderate, safety Good, cost $$$, Low to use
- CJC-1295/Ipamorelin — effectiveness Moderate, safety Good, cost $$, Medium to use
Adverse effects
Common:
- Dose-dependent nephrotoxicity: transient elevations in creatinine and BUN observed in >50% of non-human primates at therapeutic doses; mechanism likely involves renal tubular peptide fragment accumulation
- Injection site reactions: erythema, induration, and transient pain at subcutaneous administration sites
Rare:
- Severe acute kidney injury at supraphysiologic doses in primate studies — requiring dose reduction or discontinuation; incidence and severity increased with dose escalation above ~250 mcg/kg/day
Contraindications & risk mitigation
Contraindicated in:
- Individuals with CKD stage 2 or higher (eGFR <90 mL/min/1.73m²)
- Patients on concurrent nephrotoxic agents (aminoglycosides, NSAIDs, iodinated contrast)
- Individuals with active thrombotic or vascular disorders
- Immunocompromised patients due to unknown immunological sequelae of vascular apoptosis
- Serial monitoring of renal function (serum creatinine, BUN, urinalysis with microscopy) at baseline, weekly during protocol, and 2 weeks post-cycle
- Aggressive hydration protocol (minimum 40 mL/kg/day) to facilitate renal clearance of apoptotic peptide fragments
- Dose titration beginning at 50–100 mcg/kg/day with incremental escalation based on renal tolerance
- Avoid concurrent use of all nephrotoxic substances including OTC NSAIDs and contrast agents during the cycle window
Qué hace
Reduction in visible fat, particularly around the abdomen and waist; possible improvement in blood sugar levels; potential weight loss on the scale.
Cómo funciona
Think of your body's fat tissue like a neighborhood that depends on a network of water pipes. Adipotide is like a specialized crew that identifies only the pipes leading to the unwanted neighborhood, cuts them off, and causes that district to wither away — leaving the rest of the city (your healthy tissues) untouched.
After a subcutaneous injection, Adipotide circulates in the bloodstream and docks onto a protein called prohibitin, which is found almost exclusively on the walls of blood vessels inside fat tissue. Once attached, it triggers those cells to self-destruct, cutting off the fat depot's blood supply and causing fat cells to die.
Qué esperar
In primate studies, measurable fat loss was observed within the first 1–2 weeks of daily dosing. Humans have not been formally studied, so onset is unknown.
- Week 1: Peptide begins binding to adipose vasculature. Some users may notice slight injection site reactions. Kidney labs should be checked at baseline.
- Weeks 2-4: Fat reduction may become visible, especially in visceral/abdominal areas. Energy levels may fluctuate. Kidney markers should be monitored weekly.
- Weeks 4-8: In primate studies, significant body fat percentage reduction was maintained post-cycle. Long-term human outcomes are unknown. Post-cycle kidney recovery should be confirmed with labs.
Bueno saber
- Stay well-hydrated throughout the cycle — drink at least 2–3 liters of water daily
- Monitor kidney function (creatinine, BUN, eGFR) via blood tests before, during, and after any research protocol
- Start with the lowest possible dose and assess tolerance before escalating
Manteniéndose seguro
- Kidney stress — the most important risk, showing up as changes in urine and lab values
- Injection site redness or swelling
- Fatigue and tiredness during the cycle
- Mild dehydration
Evitar si tienes:
- Anyone with kidney problems or a history of kidney disease
- Pregnant or breastfeeding women
- People taking medications that are hard on the kidneys
Mecanismo de acción
Adipotide is a bimodal chimeric peptide consisting of a vascular-homing domain CKGGRAKDC that binds prohibitin (PHB) — a mitochondria-associated protein aberrantly translocated to the luminal surface of white adipose tissue endothelium — fused via a GG dipeptide linker to the pro-apoptotic sequence D(KLAKLAK)2. PHB surface expression on WAT vasculature provides tissue-specific targeting selectivity. Upon receptor-mediated endocytosis and internalization, the KLAKLAK domain disrupts mitochondrial membrane integrity via direct interaction with the inner mitochondrial membrane phospholipids, triggering cytochrome c release, caspase cascade activation, and ultimately apoptosis of the endothelial cells. This vascular ablation induces ischemic necrosis and apoptosis in dependent adipocytes, with consequent reduction in fat depot volume. Selectivity for WAT over brown adipose tissue (BAT) vasculature and other organ vasculature appears to stem from differential PHB cell-surface expression patterns.
Following subcutaneous injection, the peptide enters systemic circulation with rapid distribution. The CKGGRAKDC moiety demonstrates ligand-receptor binding affinity for PHB at the luminal endothelial surface of WAT-feeding vessels. Following internalization via endocytosis, the D(KLAKLAK)2 domain inserts into and disrupts mitochondrial membranes, triggering intrinsic apoptosis. Vascular collapse leads to downstream ischemic adipocyte death. Renal filtration of peptide fragments and metabolic byproducts is believed to be responsible for the observed nephrotoxic effects, possibly via tubular accumulation.
Farmacodinamia
Pharmacodynamic effects on adipose vasculature likely begin within hours of the first dose based on peptide-receptor binding kinetics. Histological evidence of apoptotic endothelial cells was observed within 24–72 hours in murine models. Measurable fat mass reduction in rhesus macaques was observed at 4 weeks with daily dosing.
Reduction in fat depot volume (particularly visceral WAT), decreased plasma leptin, improved insulin sensitivity, reduced BMI — all documented in non-human primate studies. Concomitant rise in serum creatinine and BUN reflects renal stress that reversed upon discontinuation in study animals (at lower doses).
Cronología
- Days 1-3: Initial receptor engagement; PHB-binding of CKGGRAKDC domain on WAT endothelium; endothelial apoptosis begins; baseline kidney labs essential before initiation.
- Weeks 1-2: Progressive vascular collapse in WAT depots; adipocyte ischemia and apoptosis underway; measurable reduction in fat depot MRI volume reported in primate studies by day 14; creatinine elevation may begin — monitor closely.
- Weeks 2-8: Sustained reduction in WAT volume; improved insulin sensitivity and reduced leptin levels in primate studies; renal stress peaks and should stabilize or decline upon dose reduction; post-cycle labs confirm recovery of renal indices.
Comparaciones
- FTPP Adipotide — efectividad High, seguridad Caution, costo $$$, Medium de usar
- AOD-9604 — efectividad Moderate, seguridad Good, costo $$, Medium de usar
- Tesamorelin — efectividad Moderate, seguridad Good, costo $$$, Low de usar
- CJC-1295/Ipamorelin — efectividad Moderate, seguridad Good, costo $$, Medium de usar
Efectos adversos
Comunes:
- Dose-dependent nephrotoxicity: transient elevations in creatinine and BUN observed in >50% of non-human primates at therapeutic doses; mechanism likely involves renal tubular peptide fragment accumulation
- Injection site reactions: erythema, induration, and transient pain at subcutaneous administration sites
Raros:
- Severe acute kidney injury at supraphysiologic doses in primate studies — requiring dose reduction or discontinuation; incidence and severity increased with dose escalation above ~250 mcg/kg/day
Contraindicaciones y mitigación de riesgos
Contraindicado en:
- Individuals with CKD stage 2 or higher (eGFR <90 mL/min/1.73m²)
- Patients on concurrent nephrotoxic agents (aminoglycosides, NSAIDs, iodinated contrast)
- Individuals with active thrombotic or vascular disorders
- Immunocompromised patients due to unknown immunological sequelae of vascular apoptosis
- Serial monitoring of renal function (serum creatinine, BUN, urinalysis with microscopy) at baseline, weekly during protocol, and 2 weeks post-cycle
- Aggressive hydration protocol (minimum 40 mL/kg/day) to facilitate renal clearance of apoptotic peptide fragments
- Dose titration beginning at 50–100 mcg/kg/day with incremental escalation based on renal tolerance
- Avoid concurrent use of all nephrotoxic substances including OTC NSAIDs and contrast agents during the cycle window
Reference data
Specifications
- Molecular formula
- C83H142N24O20S2 (approximate for core peptide; varies with salt form)
- Molecular weight
- ~1874 Da (approximate)
- Half-life
- ~1–2 hours (estimated based on peptide pharmacokinetics; not formally established in humans)
- Route
- Subcutaneous
- Cycle length
- 4–28 days (primate studies used cycles of 4–28 days; optimal human cycle unknown)
- Storage
- Lyophilized powder: store at -20°C, protected from light and moisture. Reconstituted solution: refrigerate at 2–8°C, use within 7–10 days, do not freeze reconstituted product.
- Legal status
- Research compound only; not approved by the FDA, EMA, or any major regulatory agency for human use. Legal to possess in many jurisdictions for research purposes but not for human administration.
FAQ
Common questions
What is the significance of prohibitin (PHB) as a vascular target?
PHB is normally an intracellular mitochondrial chaperone protein but undergoes aberrant translocation to the cell surface of endothelial cells specifically within WAT vasculature. This tissue-restricted surface expression provides the molecular basis for Adipotide's selectivity. The original phage display screening work by Kolonin et al. (2004, Nature Medicine) identified CKGGRAKDC as a WAT-homing peptide via this mechanism.
What does the non-human primate study show quantitatively?
Barnhart et al. (2011, Science Translational Medicine) reported that obese rhesus macaques treated with Adipotide over 28 days showed approximately 11% reduction in body weight, 27% reduction in BMI, and significant reductions in waist circumference compared to controls. Improvements in HOMA-IR (insulin resistance index) were also reported. Nephrotoxicity was reversible at doses used but was the primary safety concern.
Is there any human clinical trial data?
As of the available literature, only very early-phase or exploratory human data has been described in conference settings related to prostate cancer patients (as a secondary anti-obesity endpoint), but no completed published Phase I/II trial exists in the open literature for obesity as the primary indication. All metabolic efficacy data remains at the animal level.
What is the evidence level?
This compound is classified as Animal data. Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.
Research
Research & sources
Current evidence for FTPP Adipotide is rated as Animal data. Research is based primarily on animal models.
- 1. Reversal of obesity by targeted ablation of adipose tissue (2004) — Kolonin MG et al., Nature Medicine 10(6):625-632. doi:10.1038/nm1048
- 2. Targeted apoptosis of adipose vasculature as an experimental therapy for obesity and metabolic disorders (2011) — Barnhart KF et al., Science Translational Medicine 3(108):108ra112. doi:10.1126/scitranslmed.3002155
- 3. Prohibitin as a surface marker for targeting adipose vascular endothelium (2014) — Salameh A et al., related context from vascular biology literature
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