Adipotide (Prohibitin‑TP01)
Prohibitin‑Targeting Peptidomimetic | Experimental Anti‑Obesity
Adipotide (Prohibitin‑TP01) is a chimeric, adipose‑vasculature–targeted peptidomimetic that homes to prohibitin/annexin A2 on white adipose tissue endothelium and delivers a pro‑apoptotic D‑(KLAKLAK)2 motif. In obese primates it produced rapid fat loss with improved insulin resistance, but development halted after an early Phase 1 oncology trial; kidney safety signals (reversible proximal tubule changes) remain a key concern.
Daily dose
0.43 mg/kg (research primate dose)
Frequency
Once daily
Cycle length
28 days (research), then recovery
Storage
-20°C (lyophilized); 2–8°C (reconstituted)
Key benefits
Demonstrated rapid weight and fat‑mass reduction with improved insulin resistance in obese non‑human primates.
How it works
CKGGRAKDC adipose‑homing ligand targets prohibitin/annexin A2 on WAT endothelium; linked D‑(KLAKLAK)2 induces local apoptosis → reduced perfusion and adipocyte loss.
Dosage protocols
Goal
Primate research (fixed‑dose)
Dose
0.43 mg/kg · Once daily
Route
Subcutaneous
Goal
Primate dose‑finding
Dose
0.10–0.75 mg/kg · Once daily
Route
Subcutaneous (escalation)
Research indications
weight Loss
metabolic
appetite Control
Administration
Interactions
Safety notes
Investigational compound; not FDA‑approved.
Kidney monitoring required in animal studies (creatinine, urinalysis).
Avoid dehydration; consider pausing with persistent creatinine rise.
No pregnancy/lactation data.
Research studies
Human adipose targeting – imaging validation (2018)
Human adipose tissue (ex vivo) & mouse in vivo | CKGGRAKDC MRI probe | Single/short courses | Specific WAT targeting demonstrated
Molecular MRI using CKGGRAKDC confirmed prohibitin‑based adipose targeting, supporting the translational targeting concept.
View study →Obese rhesus macaques – fixed‑dose efficacy & safety (2011)
Rhesus macaques | 0.43 mg/kg SC daily | 28 days + 28‑day recovery | 7.4–14.7% weight loss; insulin resistance improved; mild, dose‑dependent, reversible proximal tubule changes
White‑adipose vasculature targeting led to rapid fat mass reduction and improved insulin dynamics. Kidney signals (creatinine rise, tubular changes) were dose‑related and largely reversible after discontinuation.
View study →Rhesus macaques – dose‑finding (2011)
Rhesus macaques | 0.10 → 0.25 → 0.43 → 0.75 mg/kg SC (escalated) | 63 days total | Dose‑dependent efficacy; renal safety signal >0.25 mg/kg
Identified 0.43 mg/kg SC daily as the optimal primate dose balancing efficacy and renal safety for subsequent fixed‑dose testing.
View study →First‑in‑human Phase 1 (oncology/weight) – terminated (2010–2013)
Adults with metastatic prostate cancer & obesity | Subcutaneous, dose‑escalation | Early termination; limited enrollment
Single‑center Phase 1 (MD Anderson) of Prohibitin‑TP01 in advanced prostate cancer patients with obesity; development discontinued before efficacy read‑out.
View study →Rodent proof‑of‑concept – targeted adipose vascular ablation (2004)
Mice (diet‑induced obesity) | CKGGRAKDC‑GG‑D(KLAKLAK)2 | Daily x 4 weeks | ~30% weight reduction; adipose vascular apoptosis; metabolic normalization
In vivo phage display identified CKGGRAKDC as a white‑fat vasculature 'ZIP code' (prohibitin receptor). Fusing this ligand to D‑(KLAKLAK)2 induced targeted apoptosis and robust fat loss.
View study →