Adipotide Research, Specifications & Scientific Information

Adipotide is an investigational chimeric peptidomimetic that joins a vascular homing peptide to a proapoptotic sequence built from D-amino acids. Its published evidence is preclinical; the single registered human trial was terminated after four participants and has never reported. It is not approved by the FDA for any use.

By Published Updated

Category: Fat and metabolic research peptides

Introduction

Adipotide is not a hormone analogue and does not act at a receptor. It is a delivery construct: a short peptide that binds a marker on the blood vessels supplying white adipose tissue, welded by a two-glycine linker to a sequence that kills whatever cell it gets into.

That design comes from a 2004 paper that did three things at once — isolated a homing motif by in vivo phage display, identified prohibitin as the protein it binds, and showed that attaching a proapoptotic peptide to that motif ablated white fat in mice [1]. A 2011 study extended the work to obese monkeys and reported both an effect and a limit: reversible changes in renal proximal tubule function at the amounts identified as optimal [2].

What this page mostly has to record is what came next, which is very little. The mechanistic interpretation of the monkey study was challenged in print [3]. A single first-in-human trial was registered and terminated after four participants, and has never published a result [4]. The compound's substantive evidence base has not grown since 2011. That is a short page, and it should be.

This page is a reference record. It sets out what has been published about adipotide's structure, its molecular target and the preclinical literature, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time the page was built. It describes research. It does not describe use in people or animals, and it carries no guidance of any kind on handling the material.

What Is Adipotide?

Adipotide is an investigational synthetic peptidomimetic, written in the literature as CKGGRAKDC-GG-D(KLAKLAK)2 and also referred to as a fat-targeted proapoptotic peptide or as prohibitin-targeting peptide 1. It is not an approved medicine in the United States and has not been approved by the U.S. Food and Drug Administration for any indication.

It does not belong to any of the hormone families that dominate this category. It is not an analogue of a natural peptide, it has no endogenous counterpart, and it has no receptor in the pharmacological sense. It is a chimera of two functional parts, each drawn from a different line of work:

  • CKGGRAKDC — a nine-residue vascular homing peptide, cyclised through its two cysteines, isolated by in vivo phage display for its ability to home to white fat vasculature [1].
  • (KLAKLAK)2 — a fourteen-residue amphipathic sequence that disrupts mitochondrial membranes and initiates apoptosis, built entirely from D-amino acids.

The construct is therefore best described as a targeting system rather than as a drug acting on a pathway.

Adipotide Specifications

Compound name
Adipotide
Full chemical name
CKGGRAKDC-GG-D(KLAKLAK)2
Aliases
FTPP, fat-targeted proapoptotic peptide, prohibitin-targeting peptide 1, PTP-1
Development code
PTP-1
CAS number
859216-15-2
PubChem CID
163360068
UNII
Not publicly characterised
Compound type
Synthetic chimeric peptidomimetic containing D-amino acid residues
Peptide family
Not a hormone analogue. A ligand-directed chimeric construct: a vascular homing peptide joined to a proapoptotic amphipathic sequence
Amino acid sequence
Not publicly characterised
Sequence length
Not publicly characterised
Molecular formula
C111H206N36O28S2
Molecular weight
2557.2 g/mol
Primary target
Prohibitin on the vascular endothelium of white adipose tissue
Secondary targets
Mitochondrial membranes, through the proapoptotic segment of the construct
Receptor family
Not a G protein-coupled receptor ligand. Prohibitin is a multifunctional membrane protein, not a classical signalling receptor
Agonist / antagonist status
Neither agonist nor antagonist. The homing segment binds a surface marker and the construct acts by initiating apoptosis in the cell it is delivered to

Adipotide has no single-letter amino acid sequence that can honestly be published, which is why that field is left as unknown rather than filled. The published construct is written CKGGRAKDC-GG-D(KLAKLAK)2 and has three parts. CKGGRAKDC is a nine-residue homing peptide isolated by in vivo phage display, cyclised through its two cysteines, that binds prohibitin on the vasculature of white adipose tissue. GG is a two-residue glycine linker. (KLAKLAK)2 is a fourteen-residue amphipathic sequence that disrupts mitochondrial membranes and initiates apoptosis — and it is synthesised entirely from D-amino acids, which is what the prefixed D denotes. Single-letter code has no way to mark a D-residue, so writing the construct as a plain 25-letter string would describe a different and inactive molecule; the D-configuration is what makes the proapoptotic segment resistant to proteolysis and is not a formatting detail. No UNII is recorded for adipotide in the FDA/NCATS Global Substance Registration System. The molecular formula and mass shown are those carried by PubChem CID 163360068, alongside CAS registry number 859216-15-2. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Adipotide Work?

The mechanism has two steps, and neither of them involves an adipocyte.

Step one is address. Prohibitin is a multifunctional membrane protein. The 2004 work established it as a vascular marker of adipose tissue — expressed on the endothelium of the blood vessels that supply white fat, and accessible from the bloodstream. The CKGGRAKDC motif associates with it. That is what makes the construct selective: its proapoptotic half has no selectivity of its own [1].

Step two is payload. (KLAKLAK)2 is amphipathic and disrupts mitochondrial membranes; it is inert outside a cell and lethal inside one. The D-amino acid configuration exists so that the segment survives long enough in circulation to be delivered.

The consequence reported in animals is ablation of the vasculature supplying white adipose tissue, with resorption of the tissue following from the loss of its blood supply [1]. This is a fundamentally different proposition from the receptor agonists elsewhere in this library: it does not modulate a signalling pathway, it destroys a tissue compartment, and the questions it raises are questions about targeting fidelity and off-target delivery rather than about receptor selectivity or duration of action.

Adipotide Mechanism of Action

In vitro research

The target identification is the part of this compound's record that has held up best, because it is a straightforward biochemical and histological claim rather than an inference from a physiological outcome.

The homing motif was isolated by in vivo phage display — a selection method that screens a library of peptide-displaying phage in a living animal and recovers those that accumulate in a chosen tissue. The motif recovered for white fat vasculature was CKGGRAKDC. The peptide was then shown to associate with prohibitin, and prohibitin was established as a vascular marker of adipose tissue [1].

One further observation in that paper carries the translational weight: prohibitin is also expressed in the blood vessels of human white fat [1]. That is a statement about human tissue, and it is the only human-tissue evidence in this compound's published record. It establishes that the target exists in people. It establishes nothing about what happens when the construct is administered to one.

Analytical characterisation of supplied material is a separate exercise. For a construct of this kind it has an additional requirement over a conventional peptide: the D-configuration of the proapoptotic segment and the disulfide cyclisation of the homing segment both have to be confirmed, and neither is visible in a molecular mass alone.

What Is Adipotide Being Researched For?

The published research record is narrow and is almost entirely preclinical:

  • Adipose tissue vasculature and prohibitin biology — target identification and ablation in mice [1].
  • Metabolic and body-composition change in non-human primates — a study in obese Old World monkeys, including a renal safety finding [2].
  • Metastatic prostate cancer with obesity — the single registered first-in-human trial, terminated [4].

No active clinical development programme for this compound is identifiable from the literature and trial registries cited on this page, and the most recent primary study in the record dates from 2011.

Human Research on Adipotide

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

There is one entry to make here, and it is a negative one.

A single first-in-human study was registered: a phase 1 evaluation of a single cycle of prohibitin-targeting peptide 1 in participants with metastatic prostate cancer and obesity. The registry record shows the trial was terminated, after enrolling four participants [4].

No results from that trial have been published in the literature indexed on this page. There is therefore no published human pharmacokinetic profile for adipotide, no published human safety dataset, and no published human efficacy result of any kind.

Two things follow, and they bound everything else on this page. Claims about what this compound does in people have no published human source to rest on. And the renal proximal tubule finding described in the preclinical section below — the one limit the animal work identified clearly — has never been characterised in a person.

Preclinical Research on Adipotide

Animal research

Mice

The 2004 study reported that targeting the proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat. Established white adipose tissue was resorbed, and the authors describe normalisation of metabolism and reversal of obesity in the model, without detectable adverse effects [1].

"Without detectable adverse effects" is a phrase worth reading precisely. It is a statement about what a 2004 mouse study looked for and did not find, in an animal, over that study's duration — not a safety finding.

Monkeys

The 2011 study was designed specifically to address the gap that defeats most anti-obesity work discovered in rodents: the biological differences between rodents and primates. It evaluated the construct in obese Old World monkeys [2].

The reported findings were targeted apoptosis within the blood vessels of white adipose tissue, with magnetic resonance imaging and dual-energy x-ray absorptiometry confirming a marked reduction in white adipose tissue, alongside improvement in insulin resistance [2].

The same paper reports the limit. At the amounts determined experimentally to be optimal, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function [2]. A targeting construct that reaches the kidney is a targeting construct that is not fully selective, and the proximal tubule is where a filtered peptide would be expected to accumulate.

The published challenge

The mechanistic interpretation of the monkey study did not go unchallenged. A comment published in the same journal argued that the reported effect might reflect a direct effect of the construct on food consumption rather than the vascular apoptosis mechanism proposed [3].

That challenge matters more here than a comment usually would, because the whole rationale for this compound is mechanistic. If the observed change in obese monkeys is attributable to reduced food consumption, then the targeting architecture — the part that makes adipotide interesting — is not what produced the result. The exchange is part of the published record and is cited here rather than omitted.

Findings described in this section were observed in animals. Mouse and non-human primate models of obesity are standard preclinical tools, and nothing in them establishes anything about humans.

Current Research Status

Regulatory status (United States)
Not approved. Adipotide is an investigational compound and has not been approved by the U.S. Food and Drug Administration for any indication.
Investigational status
Not in active clinical development in any programme identifiable from the published literature and trial registries cited on this page. One first-in-human trial was registered and was terminated after enrolling four participants, and no results from it have been published. The published record is otherwise preclinical and its most recent primary study dates from 2011.
Highest research phase reached
Phase 1 registered and terminated after four participants, with no published results; the substantive published evidence is preclinical
Approved uses
None
Approval is compound-specific
No

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

Adipotide is the reason the specification table above shows no amino acid sequence, and the reason is not that the sequence is unpublished. It is that publishing it as a single-letter string would be wrong.

The proapoptotic segment is D-configured, and single-letter code cannot say so. (KLAKLAK)2 is synthesised entirely from D-amino acids. A peptide of those same fourteen letters in the ordinary L-configuration is a different molecule — one that circulating proteases degrade, and that would not deliver a payload anywhere. The D-configuration is the functional feature, not a notational one, and a sequence field that cannot express it should be left empty rather than filled misleadingly. The full published construct notation, CKGGRAKDC-GG-D(KLAKLAK)2, appears in the specification notes above.

The homing segment is cyclic. CKGGRAKDC carries cysteines at both ends and is cyclised through them. A linear nine-residue peptide of those letters is not the motif that was selected by phage display.

The identifiers are thin and partly absent. CAS registry number 859216-15-2 and PubChem compound identifier 163360068 both resolve, and PubChem carries the molecular formula C111H206N36O28S2 at approximately 2,557.2 g/mol. No UNII is recorded in the FDA/NCATS Global Substance Registration System — a substance register entry generally follows regulatory engagement, and for a compound whose only registered trial was terminated in phase 1, its absence is unsurprising rather than anomalous. The field is published as unknown rather than filled.

Frequently Asked Questions

What is adipotide?
Adipotide is a synthetic chimeric peptidomimetic written CKGGRAKDC-GG-D(KLAKLAK)2. The first segment is a homing peptide isolated by in vivo phage display that binds prohibitin on the vasculature of white adipose tissue; the second is a proapoptotic amphipathic sequence built from D-amino acids [1, 2]. It is investigational and has not been approved by the U.S. Food and Drug Administration for any indication.
How does adipotide work?
It is a delivery construct rather than a receptor ligand. The homing segment binds prohibitin, which the discovery paper established as a vascular marker of adipose tissue; the proapoptotic segment then initiates apoptosis in the cells the construct reaches. In mice, targeting the proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat [1]. Nothing in that mechanism acts on adipocytes directly — the reported target is the blood supply.
Why does adipotide have no published amino acid sequence on this page?
Because a single-letter string would be wrong. The proapoptotic segment is synthesised from D-amino acids, and single-letter code has no way to mark a D-residue. Writing the construct as a plain 25-letter string would describe a different molecule — one whose proapoptotic segment would be degraded rather than active. The full published construct notation is given in the specification notes above instead.
Has adipotide been studied in humans?
One first-in-human trial was registered: a phase 1 evaluation of a single cycle of prohibitin-targeting peptide 1 in participants with metastatic prostate cancer and obesity. The registry record shows it was terminated after enrolling four participants [4]. No results from it have been published in the literature cited on this page. There is no published human pharmacokinetic, safety or efficacy dataset for this compound.
What did the monkey study find, and was it disputed?
In obese Old World monkeys, the construct was reported to induce targeted apoptosis within the blood vessels of white adipose tissue, with imaging confirming a marked reduction in white adipose tissue and with improvement in insulin resistance. At the amounts identified experimentally as optimal, monkeys of three species showed predictable and reversible changes in renal proximal tubule function [2]. The mechanistic interpretation was challenged in a published comment in the same journal, which argued that the observations might instead reflect a direct effect of the construct on food consumption [3].
Is adipotide still in development?
No active clinical programme is identifiable from the published literature and trial registries cited on this page. The most recent primary study in the record dates from 2011, and the single registered human trial was terminated. This page describes a compound whose evidence base stopped growing more than a decade ago.
Is adipotide FDA approved?
No. Adipotide is an investigational compound. It has not been approved by the U.S. Food and Drug Administration for any indication.
What identifiers are published for adipotide?
CAS registry number 859216-15-2 and PubChem compound identifier 163360068, which carries the molecular formula C111H206N36O28S2 at approximately 2557.2 g/mol. No UNII is recorded for adipotide in the FDA/NCATS Global Substance Registration System, so that field is published as unknown rather than estimated.

Scientific References

  1. Kolonin MG, Saha PK, Chan L, et al.. Reversal of obesity by targeted ablation of adipose tissue Nature medicine; 2004. PMID 15133506 doi:10.1038/nm1048
  2. Barnhart KF, Christianson DR, Hanley PW, et al.. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys Science translational medicine; 2011. PMID 22072637 doi:10.1126/scitranslmed.3002621
  3. Criscione L. Comment on "a peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys" Science translational medicine; 2012. PMID 22539771 doi:10.1126/scitranslmed.3003760
  4. A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity 2012. NCT01262664

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.