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Explore  /  Adipotide (FTPP / Prohibitin-TP01)
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Adipotide (FTPP / Prohibitin-TP01)

F
lead outcome
Weight loss / fat reduction (the marketed use)
grades vary by outcome ↓
Peptide
also called — Adipotide · FTPP (Fat-Targeted Proapoptotic Peptide)
fat loss (vascular-ablation)anti-obesity(originally oncology / anti-angiogenic)

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.

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.

Legal standing, by region
European Union
Not approved

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

Evidence, by outcome
How we grade →

An honest grade per outcome — drawn from the evidence, not any catalogue. Hype and undemonstrated marketing claims grade low.

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

Vallydia sells its own cosmetic serums, and some ingredients graded here belong to the same categories as those products. Grades are drawn from the published evidence by the method we publish, and applied to our own ingredients on the same terms — our copper-peptide serum is graded no more kindly than the peptides it competes with. We disclose the interest so you can weigh it.

Trade names shown here (for example Matrixyl, Argireline, Syn-Ake) are the property of their respective owners and are used only to identify the ingredient under discussion. Their appearance implies no affiliation with, or endorsement by, the proprietor.

Evidence changes

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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.

Chemical identifiers

Cross-reference identifiers for the authoritative external databases — not a recipe, and nothing about how to use it.

PubChem CID163360068
InChIKeyGZESIPHLGJDZRG-VCWDIOOSSA-N
SMILESC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)NCC(=O)NCC(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](C)C(=O)N[C@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N

via PubChem exact-name match (Adipotide) · high confidence

Sources — 5 cited
01Kolonin 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.
02Barnhart 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).
03Rupnick MA, et al. Adipose tissue mass can be regulated through the vasculature. PNAS. 2002 (proof-of-concept).
04Arrowhead 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).
05Daquinag AC, Zhang Y, Kolonin MG. Vascular targeting of adipose tissue. Trends Pharmacol Sci. 2011 (review); subsequent "hunter-killer" peptide work (D-WAT/D-CAN).
Updated 2026-07-13 (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)

Grades reflect the published evidence, not our interest. No dosing, reconstitution, or administration is published for research compounds — that restraint is deliberate.

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