Adipotide (FTPP / Prohibitin-TP01)
Adipotide (FTPP) — the fat-vasculature-killing peptide that failed on kidney toxicity: the full story

Class: peptide
Synonyms: Adipotide
FTPP (Fat-Targeted Proapoptotic Peptide)
Function tags: fat loss (vascular-ablation)
anti-obesity
(originally oncology / anti-angiogenic)
Overall evidence grade: C
WADA prohibited: no
Last updated: 2026-07-13

In brief: Adipotide (FTPP) is a synthetic two-part peptide that works unlike any other fat-loss compound here: instead of curbing appetite or tweaking metabolism, it selectively destroys the blood vessels that feed white fat, so the fat cells lose their blood supply and die. One half (CKGGRAKDC) homes to prohibitin on fat's vasculature; the other (D(KLAKLAK)₂) triggers apoptosis. The story is remarkable: it grew out of cancer research (starving tumors of blood), produced ~11% weight loss in obese monkeys with big insulin-sensitivity gains (Science Translational Medicine, 2011), and reached a human Phase 1 trial run by Arrowhead/MD Anderson in obese prostate-cancer patients. But the monkey study had already flagged kidney changes, and in humans the trial was terminated for nephrotoxicity; development was permanently discontinued in 2019 with no published human results. It's the register's boldest concept and one of its clearest safety-failure lessons: a genuinely innovative mechanism that the kidneys couldn't tolerate. Still sold gray-market — which is exactly why the honest record matters.

## Identity a **synthetic chimeric peptidomimetic** built from two functional halves joined by a Gly-Gly linker. The first — **CKGGRAKDC** — is a **homing domain** that binds **prohibitin** (and annexin A2) on the endothelial cells lining the **blood vessels of white adipose tissue**. The second — **D(KLAKLAK)₂** — is a **pro-apoptotic "warhead"** that, once internalized, disrupts the mitochondrial membrane and triggers **programmed cell death**. So Adipotide is a **targeted vascular-disrupting agent**: it finds fat's blood vessels and kills them. ## Mechanism (as proposed) Adipotide is a **ligand-directed "homing + kill" peptide.** Its **CKGGRAKDC** domain recognises **prohibitin** (with annexin A2), proteins unusually enriched on the **luminal endothelium of white-adipose blood vessels** — giving it selectivity for fat's vasculature. Once bound, the **D(KLAKLAK)₂** payload is internalized, where it **disrupts the mitochondrial membrane and triggers apoptosis** in those endothelial cells. As the vessels feeding a fat depot are progressively **ablated**, the **fat cells downstream lose their blood supply and undergo secondary death**, and the fat is reabsorbed. It's a fundamentally different anti-obesity strategy — **infrastructure demolition** rather than metabolic signalling. Elegant and validated in animals; the problem was **selectivity in practice** — the kidneys (with their rich, filtration-heavy vasculature) bore toxicity.

Evidence grades by outcome:
outcome: Weight loss / fat reduction (the marketed use)
grade: F
base: Strong preclinical: mice (Nat Med 2004) + obese rhesus monkeys ~11% body weight/28 d (Sci Transl Med 2011)
caveat: Dramatic in animals, but the human trial was terminated for toxicity before any efficacy was established/published
outcome: Insulin sensitivity / metabolic
grade: F
base: Monkey: ~50% less insulin needed post-treatment
caveat: Preclinical only; never confirmed in humans
outcome: Human efficacy
grade: F
base: Phase 1 (2012), obese prostate-cancer patients — terminated; no published efficacy
caveat: The one human trial ended early on safety; efficacy in humans is unknown
outcome: Safety (the decisive issue)
grade: F
base: Nephrotoxicity — dose-dependent renal-tubular changes (monkey) → human Phase 1 terminated for kidney toxicity → discontinued 2019
caveat: This is the defining fact: a documented, trial-ending kidney-toxicity signal. Not theoretical — it stopped the program
outcome: Mechanism / target validation
grade: C
base: Prohibitin-homing + apoptotic ablation well-characterised preclinically; spawned "hunter-killer" peptide class
caveat: The biology is validated and influential; the drug failed clinically. Target ≠ safe drug

Legal status:
region: EU
status: Not approved
note: not approved anywhere; clinical development permanently discontinued (2019). Not a cosmetic; not on the FDA 503A list; no legal pathway for human use.

Cosmetic claims:

Note: The peptide that kills fat's blood supply — a brilliant idea that failed in humans on kidney toxicity. This is one of the register's most conceptually radical and most instructive entries. Three points: (1) it doesn't touch appetite or metabolism — it destroys the blood vessels feeding fat, starving fat cells to death; (2) it has a genuinely dramatic development arc — born from cancer research, it produced ~11% weight loss in obese monkeys, reached a human Phase 1 trial — and was terminated for nephrotoxicity (kidney damage), with clinical development permanently discontinued in 2019; (3) despite that documented kidney-toxicity failure, it's still sold gray-market for fat loss — making the honest record essential.
Status note: status: development permanently discontinued 2019 on nephrotoxicity; the mechanism lives on in oncology "hunter-killer" peptides, but Adipotide itself is not returning absent a fundamentally safer redesign

Sources:
Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004;10(6):625-632 (PMID 15133506) — the foundational paper.
Barnhart KF, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011 (the ~11%/28-day primate result + renal-tubular signal).
Rupnick MA, et al. Adipose tissue mass can be regulated through the vasculature. PNAS. 2002 (proof-of-concept).
Arrowhead Research Corporation — FDA IND clearance (Jan 2012), Phase 1 first-patient dosing (Jul 2012), obese castrate-resistant prostate cancer; trial terminated for nephrotoxicity; program discontinued 2019 (no peer-reviewed human results published).
Daquinag AC, Zhang Y, Kolonin MG. Vascular targeting of adipose tissue. Trends Pharmacol Sci. 2011 (review); subsequent "hunter-killer" peptide work (D-WAT/D-CAN).