Adipotide
Also known as: FTPP, Prohibitin-Targeting Peptide 1, CKGGRAKDC-GG-D(KLAKLAK)2
An experimental peptide that induces apoptosis in blood vessels supplying white adipose tissue, leading to targeted fat cell death and significant weight loss in animal studies.
Half-Life
Unknown (limited data)
Typical Dose
0.5-1 mg/kg
Frequency
5 days on, 2 days off
Routes
Subcutaneous
Overview
Adipotide (FTPP - Fat-Targeted Proapoptotic Peptide) is a novel experimental peptide developed at MD Anderson Cancer Center that targets and destroys fat cells through a unique mechanism. Unlike traditional weight loss compounds that affect metabolism or appetite, Adipotide works by cutting off blood supply to white adipose tissue, causing fat cells to undergo apoptosis (programmed cell death).
The peptide consists of two functional domains:
- Targeting Domain: CKGGRAKDC - binds to prohibitin on the surface of blood vessels supplying fat tissue
- Killing Domain: D(KLAKLAK)2 - a proapoptotic sequence that triggers cell death
Key Characteristics
- Origin: Synthetic peptide developed for cancer research, repurposed for obesity
- Classification: Proapoptotic targeting peptide
- Mechanism: Vascular disruption in adipose tissue
- Unique Feature: Physically destroys fat cells rather than shrinking them
- Research Status: Early experimental - limited human data
Mechanism
Primary Mechanisms
1. Prohibitin Targeting
The targeting sequence (CKGGRAKDC) binds specifically to prohibitin:
- Prohibitin is overexpressed on blood vessels in white adipose tissue
- This allows selective targeting of fat tissue vasculature
- Other tissues are relatively spared due to lower prohibitin expression
2. Vascular Disruption
Once bound to prohibitin:
- The peptide is internalized into endothelial cells
- Blood supply to adipose tissue is compromised
- Fat cells are deprived of oxygen and nutrients
- Results in adipocyte death
3. Apoptosis Induction
The D(KLAKLAK)2 domain:
- Is a mitochondrial membrane disrupting sequence
- Triggers programmed cell death
- Causes irreversible damage to targeted cells
- Results in permanent fat cell elimination
Downstream Effects
Metabolic Improvements
- Rapid reduction in fat mass
- Improved insulin sensitivity (observed in primates)
- Reduced inflammatory markers
- Potential reversal of metabolic syndrome features
Research
Research Note: Adipotide research is in early stages. The majority of data comes from mouse and primate studies. Human clinical trials have been limited and safety concerns exist.
Primate Studies
Rhesus Monkey Trial (2011)
The landmark study at MD Anderson showed:
- 28-day treatment period
- 11% reduction in total body weight
- 27% reduction in abdominal fat (MRI confirmed)
- Improved insulin sensitivity
- Effects persisted after treatment ended
Key Observations
- Dose-dependent fat loss
- No significant changes in food intake
- Rapid onset of effects
- Potential kidney effects noted (see Safety)
Rodent Studies
Mouse Models
Research demonstrated:
- Significant reduction in obesity markers
- Prevention of diet-induced obesity
- Reduction in established obesity
- Selective targeting confirmed histologically
Cancer Research Origins
Adipotide was originally developed for:
- Targeting tumor vasculature
- Starving tumors of blood supply
- Similar mechanism applied to fat tissue
- Demonstrates proof of concept for vascular targeting
Dosing
Critical Warning: Adipotide is an experimental compound with significant safety concerns, particularly regarding kidney function. It is NOT approved for human use. The following information is for research reference only.
Research Protocols
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| Primate Study | 0.5-1 mg/kg | Daily x 28 days | 4 weeks |
| Anecdotal Human (Reported) | 0.5 mg/kg | 5 days on, 2 off | 4-6 weeks |
| Conservative | 0.25 mg/kg | 3x weekly | 4 weeks |
Administration Notes
Weight-Based Dosing
- Dose is calculated based on body weight
- Higher doses increase efficacy but also risk
- Start at lower end of dosing range
Injection Protocol
- Subcutaneous injection most common
- Rotate injection sites
- Reconstitute with bacteriostatic water
- Use fresh preparations when possible
Cycle Considerations
- Limited data on optimal cycling
- Some users report intermittent dosing (5 on/2 off)
- Extended use increases kidney risk
- Monitor kidney function if used
Reconstitution
- Supplied as lyophilized powder
- Reconstitute with bacteriostatic water
- Calculate concentration for accurate dosing
- Store refrigerated after reconstitution
- Stability data limited - use promptly
Pharmacokinetics
Absorption
- Subcutaneous injection provides systemic absorption
- Rapid distribution to adipose tissue vasculature
- Peak effects may take several days to manifest
Distribution
- Targets prohibitin-expressing vasculature
- Concentrates in white adipose tissue blood vessels
- Limited data on full distribution profile
Metabolism
- Likely degraded by peptidases
- Metabolic pathway not fully characterized
- No known active metabolites
Elimination
- Half-life not well established
- Renal involvement in elimination (concern)
- Effects on fat persist beyond peptide clearance
Safety
Serious Safety Concerns: Adipotide has demonstrated potential nephrotoxicity (kidney damage) in animal studies. This is a significant concern that has limited its development.
Known Side Effects
Common/Expected
- Dehydration (due to fluid shifts)
- Transient kidney stress markers
- Injection site reactions
- Fatigue during treatment
Serious Concerns
Nephrotoxicity
- Elevated creatinine observed in primate studies
- Kidney injury is dose-dependent
- May be related to mechanism of action
- Potentially reversible but concerning
Other Potential Issues
- Unknown long-term effects
- Potential for off-target vascular effects
- Immune reactions possible
- Electrolyte imbalances
Contraindications
Absolute Contraindications
- Pre-existing kidney disease
- Diabetes with nephropathy
- Single kidney
- Pregnancy or breastfeeding
Relative Contraindications
- Cardiovascular disease
- Autoimmune conditions
- Age over 65
- Any condition affecting vasculature
Required Monitoring
If research use is undertaken:
- Baseline kidney function (BUN, creatinine, GFR)
- Weekly kidney function during use
- Urine analysis for protein/blood
- Hydration status monitoring
- Blood pressure monitoring
Comparison with Other Fat Loss Peptides
| Feature | Adipotide | AOD-9604 | Semaglutide | |---------|-----------|----------|-------------| | Mechanism | Destroys fat cells | Mimics lipolytic HGH fragment | GLP-1 receptor agonist | | Fat Cell Effect | Kills cells | Shrinks cells | Shrinks cells | | Permanence | Potentially permanent | Reversible | Reversible | | Safety Profile | Concerning | Good | Generally good | | Approval Status | Experimental | Not approved | FDA approved | | Kidney Risk | High | Low | Low |
Regulatory
Current Status
| Region | Status | |--------|--------| | United States | Not FDA approved; experimental compound | | WADA | Likely prohibited (S0 category) | | Clinical Trials | Limited; development slowed by safety concerns | | Availability | Gray market research chemical |
Legal Considerations
- Not approved for human use anywhere
- Available only as a research chemical
- Quality and purity highly variable
- Athletes: Likely prohibited
- Significant regulatory scrutiny
Clinical Development Status
Development of Adipotide has been limited by:
- Nephrotoxicity concerns
- Difficulty in dosing optimization
- Regulatory hurdles
- Need for extensive safety studies