Scientific Reference
Adipotide (Prohibitin-TP01)
Evidence profile: Preclinical, with limited uncontrolled human reports
Adipotide (Prohibitin-TP01) is a chimeric peptidomimetic designed to selectively target the vasculature of white adipose tissue (WAT). It combines a targeting sequence (CKGGRAKDC) that binds prohibitin/annexin A2 on adipose endothelial cells with a pro-apoptotic mitochondrial-disrupting motif (D-(KLAKLAK)2). The compound has been investigated primarily in preclinical obesity models, where it demonstrated rapid and targeted fat mass reduction alongside improvements in insulin sensitivity. Despite promising efficacy, development was halted following early clinical investigation due to renal safety concerns, specifically reversible proximal tubule toxicity observed in primate studies.
Mechanism of Action
Adipotide binds to prohibitin and annexin A2 receptors expressed on the endothelial cells of white adipose tissue via its CKGGRAKDC targeting sequence. Upon internalization, the conjugated D-(KLAKLAK)2 motif disrupts mitochondrial membranes, inducing apoptosis in adipose vasculature. This leads to vascular collapse within fat tissue, subsequent adipocyte loss, and overall reduction in adipose mass.
Molecular Information
- Type: Chimeric peptidomimetic (adipose-targeting + pro-apoptotic)
- Length: 18 amino acids
- Molecular weight: 2557.2 g/mol
- Molecular formula: C111H206N36O28S2