# Adipotide — Research Peptide Profile

> Adipotide (FTPP) destroyed white-fat blood vessels in obese monkeys, cutting fat 39% in 4 weeks. Kidney signals and a terminated human trial stalled it.

Source: https://peptpedia.org/peptide/adipotide | Published: 2026-09-18 | Last updated: 2026-09-18

Adipotide is a research peptidomimetic that homes to prohibitin on white-fat blood vessels and delivers a proapoptotic payload to destroy them. In obese rhesus monkeys it produced 7-15% body weight loss in 4 weeks with improved insulin sensitivity, alongside dose-dependent, reversible kidney tubule changes. Its only human trial was terminated after 4 patients; no human efficacy data exists.

## Overview

Adipotide (also called FTPP or prohibitin-TP01) is a chimeric peptidomimetic developed at the University of Texas M.D. Anderson Cancer Center. It fuses two functional domains: CKGGRAKDC, a homing peptide identified by in vivo phage display that binds prohibitin on the surface of blood vessels supplying white adipose tissue, and D-(KLAKLAK)2, a proapoptotic peptide that disrupts mitochondrial membranes once internalized. The 2004 proof-of-concept study showed that targeted ablation of adipose vasculature reversed established obesity in mice without detectable adverse effects. In 2011, obese rhesus macaques treated for 4 weeks lost 7.4-14.7% of pretreatment body weight, with imaging confirming a 38.7% average reduction in total body fat and improved insulin sensitivity. Development stalled after a first-in-human Phase 1 trial in obese patients with metastatic prostate cancer (NCT01262664) was terminated having enrolled only 4 participants, and no human results were published. A 2025 study reported next-generation mixed-chirality prohibitin-targeting peptides with improved stability, reviving academic interest in the approach.

## Molecular Profile

- **Category:** metabolic
- **Molecular formula:** C111H206N36O28S2
- **Molecular weight:** 2557.2 g/mol
- **CAS number:** 859216-15-2
- **Amino acid sequence:** CKGGRAKDC-GG-D(KLAKLAK)2
- **Also known as:** FTPP, Prohibitin-TP01, CKGGRAKDC-GG-D(KLAKLAK)2
- **Half-life:** Not characterized in published literature

## Mechanism of Action

Adipotide exploits a vascular ZIP-code system: the CKGGRAKDC motif selectively binds prohibitin, a multifunctional membrane protein that the 2004 study established as a vascular marker of white adipose tissue endothelium; prohibitin is also expressed in vessels of human white fat. After binding and internalization, the D-(KLAKLAK)2 domain, built from D-amino acids, disrupts mitochondrial membranes and triggers apoptosis of the endothelial cell. Loss of vascular supply starves the dependent adipocytes, producing white fat resorption. Because the targeting is vascular rather than central, the weight-loss effect does not depend on appetite suppression: the 2012 mouse study showed glucose tolerance improved within 2-3 days of treatment, before significant weight change and independent of food intake, suggesting adipose vasculature plays a direct role in glucose homeostasis.

## Key Research Findings

- Adipotide fuses a white-fat vascular homing peptide (CKGGRAKDC, binding prohibitin) to a proapoptotic domain (D-(KLAKLAK)2) that destroys the blood vessels supplying adipose tissue.
- In obese rhesus macaques, 28 days of 0.43 mg/kg daily produced 7.4-14.7% body weight loss and a 38.7% average reduction in total body fat, with improved insulin resistance.
- Glucose tolerance improved within 2-3 days of treatment in obese mice, independent of weight change or food intake, implicating adipose vasculature in metabolic control.
- Dose-dependent, reversible renal proximal tubule changes appeared above 0.25 mg/kg in primates, and the only human trial (NCT01262664) was terminated after 4 participants.

## Safety & Tolerability

Adipotide's defining safety issue is the kidney: dose-dependent, reversible proximal tubule changes appeared in primates at doses near the therapeutic level. All in vivo evidence is animal; the only human trial was terminated after 4 participants with no results published, so human safety is entirely uncharacterized.

**Human data status:** A single first-in-human Phase 1 trial (NCT01262664, M.D. Anderson) enrolled 4 participants with metastatic prostate cancer and obesity before being terminated per the principal investigator's request; no human safety or efficacy data was ever published.

**Regulatory status:** Not approved by any regulator; development discontinued with no active sponsor program in the public record. Sold by gray-market vendors as a research chemical without oversight.

- In obese rhesus macaques, slight-to-moderate dose-dependent serum creatinine elevations occurred at doses above 0.25 mg/kg, and monkeys showed predictable, reversible changes in renal proximal tubule function; concurrent BUN elevations were not observed. (evidence tier: animal; [PMID 22072637](https://pubmed.ncbi.nlm.nih.gov/22072637/))
- In the original 2004 mouse study, targeted ablation of adipose vasculature reversed established obesity without detectable adverse effects at the doses used. (evidence tier: animal; [PMID 15133506](https://pubmed.ncbi.nlm.nih.gov/15133506/))
- Lean rhesus monkeys treated at the therapeutic dose (0.43 mg/kg) did not lose weight, indicating the weight-loss effect requires excess white adipose tissue rather than reflecting nonspecific systemic toxicity. (evidence tier: animal; [PMID 22072637](https://pubmed.ncbi.nlm.nih.gov/22072637/))
- Published exposure covers at most 28 days of dosing with 4-week recovery; the long-term consequences of repeated adipose-vascular ablation cycles, including effects on kidney reserve, have never been studied. (evidence tier: theoretical; [PMID 22072637](https://pubmed.ncbi.nlm.nih.gov/22072637/))

## Dosing Information (Research Context)

In the obese rhesus macaque studies, adipotide was administered subcutaneously at 0.43 mg/kg once daily for 28 days, a dose selected from escalation tiers of 0.10, 0.25, 0.43, and 0.75 mg/kg increased every 2 weeks (PMID 22072637). The terminated Phase 1 trial used a starting dose of 0.03 mg/kg subcutaneously once daily for 28 days (NCT01262664). No human efficacy dosing has ever been established.

| Route | Dose | Frequency | Notes |
| --- | --- | --- | --- |
| Subcutaneous (obese rhesus macaques) | 0.43 mg/kg | Once daily x 28 days | Experimentally determined optimal dose; 4-week recovery followed (PMID 22072637) |
| Subcutaneous (primate dose-finding) | 0.10, 0.25, 0.43, 0.75 mg/kg | Once daily, escalated every 2 weeks | Renal signals emerged above 0.25 mg/kg |
| Subcutaneous (terminated Phase 1) | 0.03 mg/kg starting | Once daily x 28 days | NCT01262664; terminated after 4 participants |

## Researched Effects

- **White Fat Reduction** (evidence: moderate): Adipotide produced rapid, marked reductions in white adipose tissue across rodent and primate studies. In the original 2004 mouse work, targeting a proapoptotic peptide to adipose vasculature caused resorption of established white fat and normalization of metabolism. In obese rhesus macaques, 4 weeks of daily subcutaneous treatment at 0.43 mg/kg produced weight loss of 7.4-14.7% of pretreatment body weight versus +1.0 to -3.5% in controls, with DEXA imaging showing a 38.7% average decrease in total body fat versus 14.8% in controls and MRI confirming white adipose tissue loss. Weight and abdominal circumference began to reverse during the 4-week recovery period after dosing stopped, indicating the effect requires continued treatment.
- **Insulin Sensitivity Improvement** (evidence: moderate): Obese monkeys treated with adipotide showed improved insulin resistance alongside fat loss in the 2011 primate study, including improved responses to intravenous glucose. Mechanistic work in obese mice demonstrated that glucose tolerance improved rapidly, within 2-3 days of treatment initiation, in a weight- and food-intake-independent manner: treated animals showed reduced serum insulin and triglycerides, distinct fatty acid and acylcarnitine profiles, and reversal of high-fat-diet-induced changes in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation pathways in adipose tissue. This positions adipose endothelium as an active contributor to metabolic regulation rather than passive plumbing.
- **Target Validation for Next-Generation Analogs** (evidence: preliminary): The prohibitin-targeting concept has spawned second-generation peptides. A 2025 Journal of the American Chemical Society study engineered mixed-chirality prohibitin peptides, with the lead compound PTP-r, built by substituting D-arginine residues into the prohibitin-TP01 scaffold, showing enhanced stability and significant body weight reduction in diet-induced obese mice, acting partly through mitochondrial uncoupling. The favorable preclinical safety profile reported for these redesigned analogs suggests the adipose-vascular targeting strategy remains scientifically active more than two decades after the original discovery.

## Research Applications

- Obesity Research
- Adipose Vasculature Biology
- Prohibitin-Targeted Therapy
- Vascular Targeting Research

## Key Studies

### Reversal of obesity by targeted ablation of adipose tissue

Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W — *Nature Medicine* (2004) — [PMID 15133506](https://pubmed.ncbi.nlm.nih.gov/15133506/) | [doi:10.1038/nm1048](https://doi.org/10.1038/nm1048)

This foundational study used in vivo phage display to isolate the CKGGRAKDC peptide motif, which homes specifically to white fat vasculature, and showed it associates with prohibitin, establishing prohibitin as a vascular marker of adipose tissue. Fusing this ligand to a proapoptotic peptide ablated white fat in diet-induced obese mice: resorption of established white adipose tissue and normalization of metabolism produced rapid obesity reversal without detectable adverse effects. The authors noted prohibitin is also expressed in blood vessels of human white fat, laying the conceptual groundwork for vascular-targeted obesity treatment.

### A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys

Barnhart KF, Christianson DR, Hanley PW, et al. — *Science Translational Medicine* (2011) — [PMID 22072637](https://pubmed.ncbi.nlm.nih.gov/22072637/) | [doi:10.1126/scitranslmed.3002621](https://doi.org/10.1126/scitranslmed.3002621)

The landmark primate study evaluated adipotide (CKGGRAKDC-GG-D(KLAKLAK)2) in obese Old World monkeys. At the experimentally determined optimal dose of 0.43 mg/kg subcutaneous daily for 28 days, treated rhesus macaques lost 7.4-14.7% of pretreatment body weight versus +1.0 to -3.5% in controls, with DEXA confirming a 38.7% average decrease in total body fat and MRI showing white adipose reduction; insulin resistance improved. Dose-finding tiers of 0.10-0.75 mg/kg established the therapeutic window. Monkeys across three species showed predictable, reversible changes in renal proximal tubule function, with slight-to-moderate creatinine elevations at doses above 0.25 mg/kg. Lean monkeys at the therapeutic dose did not lose weight, indicating specificity for excess adipose tissue.

### Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium

Kim DH, Sartor MA, Bain JR, et al. — *Diabetes* (2012) — [PMID 22733798](https://pubmed.ncbi.nlm.nih.gov/22733798/) | [doi:10.2337/db11-1579](https://doi.org/10.2337/db11-1579)

This mechanistic study tested whether ablating white adipose endothelium impairs glucose regulation as a consequence of disrupting fat tissue. Instead, the proapoptotic peptide rapidly and potently improved glucose tolerance in obese mice within 2-3 days, in a weight- and food-intake-independent manner, with pair-fed controls confirming the effect was not due to reduced intake. Treated mice showed decreased serum insulin and triglycerides, and microarray analysis of adipose tissue showed reversal of high-fat-diet-induced changes in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation pathways, suggesting a direct role for adipose vasculature in glucose homeostasis.

### Mixed-Chirality Prohibitin Peptide: D-(RLARLAR)2 Enhances Stability and In Vivo Effects on Obesity

Chan LY, Weger BD, Weger M, et al. — *Journal of the American Chemical Society* (2025) — [PMID 40591817](https://pubmed.ncbi.nlm.nih.gov/40591817/) | [doi:10.1021/jacs.5c05536](https://doi.org/10.1021/jacs.5c05536)

This 2025 study engineered a new generation of prohibitin-targeting peptides for white adipose tissue, substituting D-amino acids into the prohibitin-TP01 scaffold to improve stability. The most potent compound, PTP-r (prohibitin-TP01 with D-arginine substitution), significantly reduced body weight in diet-induced obese mice and was reported to act partly through mitochondrial uncoupling, curbing adipocyte expansion with a favorable preclinical safety profile. The work demonstrates that the adipose-vascular targeting concept underlying adipotide remains an active direction in academic obesity pharmacology.

## Frequently Asked Questions

### What is adipotide and how does it work?

Adipotide (FTPP, prohibitin-TP01) is a chimeric peptide with two parts: a homing sequence (CKGGRAKDC) that binds prohibitin on the blood vessels supplying white fat, and a proapoptotic sequence (D-(KLAKLAK)2) that kills those endothelial cells after internalization. Destroying the vasculature starves the fat tissue it supplies, causing white fat resorption. Unlike GLP-1-based drugs, it does not act on appetite or incretin pathways.

### Did adipotide work in monkeys?

Yes. In the 2011 Science Translational Medicine study, obese rhesus macaques receiving 0.43 mg/kg daily for 4 weeks lost 7.4-14.7% of pretreatment body weight, with a 38.7% average reduction in total body fat on DEXA imaging, and showed improved insulin resistance. Effects partially reversed during a 4-week recovery period after treatment stopped. Notably, lean monkeys receiving the same therapeutic dose did not lose weight, indicating the effect depends on excess white adipose tissue.

### Why was adipotide's development discontinued?

The only human trial, a Phase 1 study of prohibitin-TP01 in obese patients with metastatic prostate cancer at M.D. Anderson (NCT01262664), was terminated per the principal investigator's request after enrolling only 4 participants, and no results were published. Separately, the primate studies documented dose-dependent, reversible kidney proximal tubule changes at doses above 0.25 mg/kg, a safety signal that complicated the therapeutic window. No sponsor has publicly advanced the program since.

### What were the kidney side effects of adipotide?

In rhesus monkeys, slight-to-moderate dose-dependent serum creatinine elevations appeared at doses above 0.25 mg/kg, reflecting reversible changes in renal proximal tubule function; concurrent blood urea nitrogen elevations were not observed, and most monkeys at the 0.43 mg/kg therapeutic dose maintained normal creatinine. The kidney changes resolved after discontinuation. No human renal safety data exists because the Phase 1 trial ended without published results.

### Is adipotide FDA approved or available?

No. Adipotide is not approved anywhere, and no active clinical program exists in the public record. Material sold by research chemical vendors has no regulatory oversight, and given the renal safety signal seen in primates plus the complete absence of human safety data, it carries substantial unknown risk.

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This content is for educational and research purposes only. It is not medical advice, and the compounds covered are research chemicals not approved for human use unless explicitly stated otherwise.

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