Adipotide

Description

Adipotide^TM, or Prohibitin-Targeting Peptide 1 (Prohibitin-TP01), is an anti-obesity peptide that specifically targets and kills blood vessels supplying white fat tissue. It is the peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2. Adipotide targeted the vasculature of white adipose tissue and resulted in ~30% weight reduction in obese mice over a period of 4 weeks. Therefore, unlike nonspecific angiogenesis inhibitors, adipokine is systemically targeted to the endothelium of fat through a ligand-directed mechanism and disrupts the vascular supply of white adipose tissue, at least in rodent obesity models. Moreover, an annexin A2–prohibitin receptor system targeted by adipotide has been reported recently in the white adipose tissue vasculature of human patients[1].

Safety

A daily subcutaneous injection of Adipotide (0.43 mg/kg) is the optimal therapeutic dose for spontaneously obese macaques. It was demonstrated that the dosage of Adipotide is strongly correlated with body surface area and that its relative dose migrates from smaller to larger mammalian species (including humans). And animal studies show that Adipotide treatment is generally well tolerated. The major side effect is nephrotoxicity, which is generally mild and reversible. Decreases in serum phosphorus and potassium and urinary changes, including mild to marked glucosuria, mild to moderate proteinuria, and slight to mild increases in transitional/renal epithelial cells, have been noted throughout the dosing interval.

References

[1] Kirstin F Barnhart. “A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.” Science Translational Medicine 3 108 (2011): 108ra112.