What is Adipotide?

Adipotide (also known as Prohibitin‑TP01 or FTPP) is a synthetic peptidomimetic compound developed to target fat tissue in a novel way. PubMed+3Pep-Pedia+3Peptide Initiative+3 Instead of acting via appetite suppression or metabolic stimulation, Adipotide seeks to target the vasculature of white adipose tissue (WAT) — the blood vessels supplying fat cells — and induce apoptosis (cell death) in those vessels, thereby “starving” the fat cells. Peptide Initiative+2awbi.org+2

Specifically, it binds to receptors such as prohibitin‑1 and annexin A2 (ANXA2) that are present on the endothelial cells feeding WAT, then uses a pro‑apoptotic domain (D(KLAKLAK)₂) to disrupt mitochondrial membranes, leading to the death of the endothelial cells and subsequent loss of the adipocytes they feed. Peptide Initiative+1

How Adipotide Works (Mechanism of Action)

Here is the step‑by‐step mechanism of action of Adipotide:

1. Targeting domain: The N‑terminal sequence (CKGGRAKDC) homes to the vasculature of white fat by binding to receptors like prohibitin and ANXA2. Peptide Initiative+1

2. Internalization: Once bound, the peptide is internalized into the endothelial cells of the fat‑tissue blood vessels. Peptide Initiative+1

3. Pro‑apoptotic domain activation: The C‑terminal pro‑apoptotic domain then disrupts mitochondrial membranes (via the D(KLAKLAK)₂ motif), leading to release of cytochrome c, caspase activation and apoptosis of the endothelial cell. Peptide Initiative+1

4. Vascular collapse & fat‑cell death: With the blood supply cut off, the adipocytes (fat cells) downstream lose nutrients and oxygen, leading to secondary fat‑cell death and reduction in fat mass. PubMed+1

5. Metabolic effects: Loss of WAT may improve insulin sensitivity, reduce visceral fat, and improve metabolic markers such as glucose tolerance and triglycerides. ir.arrowheadpharma.com+2PubMed+2

This mechanism differentiates Adipotide from traditional compounds that reduce appetite or increase energy expenditure; this one is essentially a vascular ablation of fat‐cell supply. awbi.org+1

Research & Evidence so Far

Animal / Pre‑clinical Data

• In obese rodents, treatment with Adipotide resulted in up to ~30% body‑weight reduction in 28 days in some models. Peptide Initiative+1

• In a study on obese rhesus monkeys (daily subcutaneous injections of 0.10‑0.75 mg/kg for 28 days), the peptide induced targeted apoptosis in WAT vessels, and animals lost ~11 % of body weight, with reductions in BMI and abdominal circumference. PubMed+1

• The same study also noted improvements in insulin resistance and reductions in fat volume measured by MRI and DEXA. PubMed

Clinical / Human Trial Status

• A Phase 1 human trial was launched (for patients with castrate‑resistant prostate cancer) to evaluate safety / tolerability, dosing, weight changes, etc. ir.arrowheadpharma.com+1

• However, clinical development was discontinued in 2019 due to concerns about nephrotoxicity (kidney toxicity) and safety signals. Peptide Initiative+1

Benefits & Promising Aspects

• Targeted fat reduction: Because it acts on blood vessels feeding white fat, it has the potential to reduce visceral fat (fat around organs) which is highly metabolically active and dangerous. PubMed+1

• Metabolic improvements: Animal data show improved insulin sensitivity, improved glucose tolerance and reduced triglycerides even before major weight loss occurred. ir.arrowheadpharma.com+1

• Non‑central nervous system mechanism: Unlike appetite suppressants, the mechanism doesn’t rely on central pathways (brain), which may reduce some side‑effect risks such as mood/behavior changes. ir.arrowheadpharma.com+1

Risks, Safety & Limitations

• Kidney toxicity: One major concern is renal (kidney) adverse effects. Preclinical primate studies reported reversible proximal tubule changes. PubMed+2pepdose.com+2

• Not approved for human use: The development was halted; it is strictly experimental / research‑use only in many jurisdictions. Peptide Initiative+1

• Unknown long‑term effects: Because human trials were limited / terminated, the long‑term safety in humans is not established.

• Injection required: In trials, the route was subcutaneous daily injection for 28 days. ir.arrowheadpharma.com+1

• Fat cell loss vs. fat‐cell shrinking: The approach removes the vascular supply and leads to fat‑cell death; this may have unknown consequences (e.g., loose skin, metabolic adjustment).

• Ethical / regulatory issues: Because of the safety signals and discontinued development, promotion for human use is risky, and many jurisdictions may consider such use off‑label or investigational.

Typical Dosing & Use‑Protocol (Research Context)

The following is for informational/research purposes only, not a recommendation.

• In primate studies: 0.10 to 0.75 mg/kg once daily subcutaneously for 28 days was used. PubMed+1

• Some resources list a dosing guide of ~4.53 µg/lb (~10 µg/kg) for a “28‑day cycle” in research contexts. Peptides

• A common protocol: 28 days on, followed by 4‑8 weeks off (in research settings) to allow for recovery. Peptide Initiative+1

Again: this remains experimental and not approved for commercial/clinical fat‐loss use.

Summary: Is Adipotide Worth It?

Adipotide is unquestionably one of the most innovative and unique approaches to fat‑loss research: rather than simply reducing appetite or burning calories, it seeks to eliminate the blood supply to fat cells. This “fat‑cell vascular targeting” mechanism holds high promise for treating obesity and its metabolic complications.

However, the “promise” comes with major caveats: the compound was discontinued in clinical development because of safety/renal concerns; it is not approved for human fat‑loss use; long‑term safety data are lacking; and it is only available in research contexts.

For a website content piece: this means you can position Adipotide as cutting‑edge, high‑potential but experimental, emphasizing both its mechanism and the reasons it’s not mainstream yet. That balanced approach tends to resonate better with searchers (and search engines).