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Catalog/Adipotide

Adipotide

Also known as FTPP · Prohibitin-targeting peptide-1 · CKGGRAKDC-GG-D(KLAKLAK)2

A fat-targeting proapoptotic peptide that destroys the blood supply of white fat — striking in animals, but discontinued in humans for kidney toxicity.

Research refreshed

Overview

Adipotide (FTPP, "fat-targeted proapoptotic peptide") is a chimeric peptide designed to attack obesity from an unusual angle: instead of curbing appetite, it kills the blood vessels that feed white fat. One end is a homing sequence (CKGGRAKDC) that binds prohibitin on the vasculature of fat tissue; the other is a proapoptotic peptide that triggers cell death once delivered. In obese primates it produced rapid, striking fat loss — but its clinical development was halted over kidney toxicity.

Background

Adipotide is one of the boldest ideas in metabolic research: treat obesity like a tumor by cutting off its blood supply. Developed at MD Anderson Cancer Center by Renata Pasqualini and Wadih Arap, it is a chimera of two peptides. The targeting half, the cyclic nonapeptide CKGGRAKDC, recognizes prohibitin displayed on the endothelial cells of the vasculature that specifically supplies white adipose tissue. The payload half, a D-amino-acid proapoptotic sequence written D(KLAKLAK)2, is harmless outside cells but disrupts mitochondrial membranes once the targeting domain gets it inside — killing the fat’s blood vessels and, with them, the fat.

In obese rhesus monkeys the results were dramatic: rapid loss of body weight and fat over a few weeks of treatment. But translating it to people ran into a hard limit. The same peptide accumulates in the kidney, and clinical development was discontinued (around 2019) because of nephrotoxicity — the gap between the fat-reducing dose and the kidney-damaging dose proved too narrow. Adipotide is not FDA-approved and is not in active clinical development; it remains an instructive, cautionary research compound.

Mechanism

A two-domain peptide: a cyclic CKGGRAKDC motif homes to prohibitin on white-adipose-tissue blood vessels, delivering a D(KLAKLAK)2 proapoptotic sequence that disrupts mitochondrial membranes and triggers apoptosis of the vascular endothelium feeding the fat.

Key research findings

  • Antiangiogenic mechanism — homes via prohibitin to the blood vessels feeding white fat and triggers their apoptosis, rather than acting on appetite.
  • Two-domain design — a cyclic CKGGRAKDC targeting motif fused to a D(KLAKLAK)2 proapoptotic peptide.
  • Primate results — produced rapid, marked weight and fat loss in obese rhesus monkeys.
  • Discontinued for nephrotoxicity — clinical development halted (~2019); the therapeutic window against kidney toxicity was too narrow.
  • Preclinical / not approved — a cautionary research compound, not FDA-approved.

How Adipotide is made

Behind every vial of Adipotide is the same exacting pipeline every research peptide runs — but the chemistry plays out differently for this molecule. Here is how Adipotide, specifically, is brought into being.

  1. On paper first

    On paper, Adipotide is C111H206N36O28S2 — about 2,557.2 daltons of precisely arranged atoms. Before a single bond is made, the target sequence, salt form, and purity threshold are written down as the contract the finished material must meet.

  2. Built residue by residue

    Adipotide is built one protected residue at a time by solid-phase synthesis, each cycle a deprotection, a coupling, and a wash. It also carries cyclization and a disulfide bridge, extra steps beyond a plain chain that add both capability and cost.

  3. Purity is won here

    The crude mixture — Adipotide plus its deletions and side products — is then separated on preparative HPLC, and where the cut is taken decides the difference between a genuinely pure peptide and a barely-passable one.

  4. Proven, then protected

    A real batch of Adipotide proves itself: identity confirmed by mass spectrometry against its ~2,557.2 Da, purity read directly off an analytical HPLC trace, water and counterion content measured. That batch-specific certificate of analysis is the only honest way to know what is actually in a vial of Adipotide — and a short, cold, accountable chain of custody is how that purity survives the trip to your bench.

Walk the full synthesis pipeline

Handling, storage & why purity is hard

Adipotide is a chimeric peptide: a disulfide-cyclized CKGGRAKDC targeting domain joined to an all-D-amino-acid D(KLAKLAK)2 proapoptotic sequence with a C-terminal amide. Assembling two chemically distinct domains, forming the disulfide correctly, and handling the D-residues make it demanding to synthesize and purify cleanly.

Don't judge a vial by its cake. A fluffy, good-looking lyophilized powder reflects bulking agents and freeze-drying parameters — not purity. Insist on a batch-specific certificate of analysis.

How peptides are made — the full pipeline

Research areas

  • Obesity (preclinical)
  • Targeted apoptosis
  • Adipose vasculature

Research-area guides

Frequently asked questions

What is Adipotide?+

Adipotide (FTPP) is a fat-targeting proapoptotic peptide that kills the blood vessels supplying white fat, developed at MD Anderson and studied for obesity in animals.

How does it work?+

A targeting sequence (CKGGRAKDC) homes to prohibitin on the vasculature of fat tissue and delivers a proapoptotic peptide that triggers those blood vessels to die — starving the fat rather than suppressing appetite.

Why was its development stopped?+

Clinical development was discontinued (around 2019) because of kidney toxicity — the peptide accumulates in the kidney and the safe dose window proved too narrow. It is not approved.

Is Adipotide approved?+

No — it is a preclinical research compound, discontinued in clinical development and not FDA-approved. This page is a research and educational reference.

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