Adipotide (FTPP /
Prohibitin-TP01)

1990s-2003

The Cancer Connection

Targeting Tumor Blood Vessels

Wadih Arap and Renata Pasqualini were working on cancer, not obesity. Tumors need blood vessels to grow — cut off the blood supply and tumors die. The researchers developed 'phage display' technology to find peptides that would home to tumor vasculature.

Their technique involved injecting billions of random peptides into mice and seeing which ones accumulated in specific tissues. Each tissue had unique markers on its blood vessels. Find the right peptide, and you could deliver drugs — or death signals — to that tissue alone.

The method worked brilliantly for tumors. But the team noticed something interesting: fat tissue also had distinctive vascular markers. What if the same approach could target obesity?

2004

The Fat Discovery

Prohibitin and the Death Peptide

In 2004, the team published a stunning paper. They had found a peptide — CKGGRAKDC — that specifically targeted blood vessels in white adipose tissue (fat). The target was prohibitin, a protein highly expressed on fat vasculature.

But finding the target was only half the problem. They needed a way to kill those blood vessels. The solution was elegant and brutal: attach a 'proapoptotic' sequence — D(KLAKLAK)2 — that would trigger cell suicide once internalized.

The combined peptide was adipotide. In obese mice, it caused 30% weight loss in just four weeks. The fat tissue literally died and was reabsorbed by the body.

2004-2010

The Mechanism

Understanding Targeted Tissue Ablation

How does adipotide work? The targeting sequence finds prohibitin on blood vessels feeding white fat. The peptide binds, gets internalized into endothelial cells, and the kill sequence disrupts mitochondria, triggering apoptosis.

When enough blood vessel cells die, the vasculature collapses. Fat cells — suddenly deprived of oxygen and nutrients — undergo ischemic death. The body's immune system clears the debris. Fat is permanently eliminated from that area.

This was different from every other weight loss approach. Not appetite suppression. Not metabolism boosting. Not blocking fat absorption. Direct, targeted fat cell death. The approach was called 'targeted tissue ablation.'

2011

The Monkey Trials

Primate Proof of Concept

Mouse results don't always translate to humans. In 2011, the team published results from obese rhesus monkeys — primates that closely mirror human obesity. The results were remarkable.

After just four weeks of treatment followed by four weeks observation, monkeys showed 11% body weight reduction and 39% decrease in fat mass. Insulin sensitivity improved significantly. Importantly, the weight stayed off during the observation period.

There was a catch: adipotide affected the kidneys. Monkeys showed changes in kidney function, though these reversed after treatment stopped. This would be the major challenge for human development.

2012-Present

The Uncertain Future

Promise and Peril

Phase I human trials were initiated to assess safety. The kidney effects seen in monkeys were a significant concern. How much kidney stress was acceptable for weight loss? The risk-benefit calculation was complex.

Adipotide development has not progressed to advanced clinical trials. The aggressive mechanism — literally killing tissue — raises safety questions that conventional weight loss drugs don't face. Yet the approach remains scientifically fascinating.

In the era of GLP-1 drugs like Ozempic achieving 15-20% weight loss with manageable side effects, adipotide's path forward is uncertain. But as a proof of concept — that fat tissue can be selectively eliminated — it remains remarkable.