Adipotide

Adipotide (CKGGRAKDC-GG-D(KLAKLAK)2) is a pro-apoptotic peptide that selectively targets and destroys the blood vessels supplying white adipose tissue (WAT). Originally developed at MD Anderson Cancer Center, it works by binding to prohibitin on the vasculature of fat tissue, triggering apoptosis of the endothelial cells feeding fat depots. Research in primates showed dramatic visceral fat loss without systemic toxicity at appropriate doses.

— 10 mg Vial —

Reconstitute: Add 3.0 mL bacteriostatic water → ~3.33 mg/mL concentration.
Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL ≈ 33.33 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C, avoid freeze-thaw cycles.

Schedule: Daily subcutaneous injections for 4–8 weeks (cautious approach due to limited human data).
Cycle Length: 4–8 weeks (based on preclinical effective treatment duration; extend with extreme caution).
Goal: Targeted reduction of fat mass via vascular targeting in adipose tissue.

Frequency: Inject once daily subcutaneously. Starts at a conservative dose with gradual escalation to mitigate potential renal side effects.

• Selective destruction of adipose tissue vasculature
• Significant visceral and subcutaneous fat loss in animal models
• Reduces obesity-related metabolic markers
• Demonstrated fat loss in obese rhesus monkeys (up to 11% body weight in 4 weeks)
• Improves insulin sensitivity secondary to fat loss
• Does not appear to affect lean muscle mass at research doses
• Targets white adipose tissue specifically — spares brown fat
• May reduce obesity-related inflammation

Adipotide contains two functional domains: a targeting domain (CKGGRAKDC) that binds to prohibitin on the endothelium of white adipose vasculature, and a pro-apoptotic domain (D(KLAKLAK)2) that disrupts mitochondrial membranes upon internalization. The result is selective apoptosis of adipose endothelial cells, cutting off blood supply to fat depots and causing fat cell death. This mechanism bypasses traditional metabolic pathways entirely, making it independent of diet or hormone manipulation.

• Nephrotoxicity — kidney damage is the primary dose-limiting toxicity
• Elevated creatinine and BUN levels during treatment
• Dehydration risk due to renal effects
• Injection site reactions
• Fatigue
• Potential liver enzyme elevation at higher doses

Renal function must be monitored closely (creatinine, BUN, urinalysis) throughout any research protocol. High fluid intake is essential to support renal clearance. Dose reduction or discontinuation required if renal markers elevate. This peptide carries significant safety concerns and requires careful research oversight.

• Pre-existing renal disease or impairment
• Dehydration or conditions affecting renal perfusion
• Pregnancy and lactation
• Hepatic impairment
• Use with other nephrotoxic compounds

• Kolonin MG et al. (2011). Reversal of obesity by targeted ablation of adipose tissue. Science Translational Medicine. DOI: 10.1126/scitranslmed.3002735
• Kolonin MG et al. (2004). Reversal of obesity by targeted ablation of adipose tissue. Nature Medicine. DOI: 10.1038/nm1048
• Kim DH et al. (2012). Synthetic ligands to prohibitin selectively target fat tissue. PNAS. DOI: 10.1073/pnas.1108710108