Adipotide (FTPP / Prohibitin-TP01)

Identity a synthetic chimeric peptidomimetic built from two functional halves joined by a Gly-Gly linker. The first — CKGGRAKDC — is a homing domain that binds prohibitin (and annexin A2) on the endothelial cells lining the blood vessels of white adipose tissue. The second — D(KLAKLAK)₂ — is a pro-apoptotic "warhead" that, once internalized, disrupts the mitochondrial membrane and triggers programmed cell death. So Adipotide is a targeted vascular-disrupting agent: it finds fat's blood vessels and kills them. ## Mechanism (as proposed) Adipotide is a ligand-directed "homing + kill" peptide. Its CKGGRAKDC domain recognises prohibitin (with annexin A2), proteins unusually enriched on the luminal endothelium of white-adipose blood vessels — giving it selectivity for fat's vasculature. Once bound, the D(KLAKLAK)₂ payload is internalized, where it disrupts the mitochondrial membrane and triggers apoptosis in those endothelial cells. As the vessels feeding a fat depot are progressively ablated, the fat cells downstream lose their blood supply and undergo secondary death, and the fat is reabsorbed. It's a fundamentally different anti-obesity strategy — infrastructure demolition rather than metabolic signalling. Elegant and validated in animals; the problem was selectivity in practice — the kidneys (with their rich, filtration-heavy vasculature) bore toxicity.