Adipotide

It's like a guided missile aimed at the supply roads feeding a city of fat cells. Brilliant on the engineering whiteboard and devastatingly effective on the test range (mice and a handful of monkeys), yet in trials the collateral damage hit the kidneys.

A chimeric peptide: the CKGGRAKDC homing motif binds prohibitin, which is over-expressed on the endothelium of white adipose tissue blood vessels, delivering the fused D(KLAKLAK)2 pro-apoptotic sequence into those endothelial cells. There it disrupts mitochondrial membranes and triggers apoptosis, ablating the fat depot's microvasculature so the white fat undergoes ischaemic resorption, reducing adiposity and improving insulin sensitivity in animal models. Rodent data also suggest a significant component of the weight loss is driven by reduced food intake.

Research contexts. Not proven uses, and not recommendations.

Effectively none for obesity. The strong data are preclinical: dramatic weight loss in diet-induced obese mice and approximately 11% body-weight loss with improved insulin sensitivity in obese rhesus monkeys (Science Translational Medicine, 2011). First-in-human Phase 1 studies were registered in oncology populations (for example NCT01262664 at MD Anderson; a separate Arrowhead Pharmaceuticals Phase 1 obesity trial began in 2012). No published efficacy or safety results emerged and the programmes did not advance.

• !Nephrotoxicity: dose-dependent renal tubular injury (raised creatinine, proteinuria, glucosuria) was reversible in monkeys but represents a serious dose-limiting toxicity signal.
• !No completed, published human efficacy or safety trial; any human use is uncontrolled experimentation.
• !Destroying fat via vascular apoptosis is non-selective in principle. The long-term consequences of ablating adipose microvasculature in humans are unknown.
• !Sold only as an unlicensed research chemical. No pharmaceutical-grade manufacturing, purity, sterility or dose-accuracy guarantees.
• !Marketing as a fat-melting peptide grossly overstates an animal-stage compound with a documented kidney risk.

Not a licensed medicine in the UK. Adipotide has no MHRA marketing authorisation and is not approved anywhere in the world. It cannot lawfully be prescribed or sold as a medicine for human use. It is an investigational early-stage research compound whose clinical development stalled. Material offered to consumers online is an unlicensed substance typically labelled 'for research use only / not for human consumption'. Supplying or marketing it for human use would fall foul of the Human Medicines Regulations 2012.

• NCT01262664· Phase 1· No published weight-loss efficacy/safety read-out; program did not advance

  A First-in-Man, Phase I Evaluation of a Single Cycle of Prohibitin-Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity

  Run at MD Anderson Cancer Center in castrate-resistant prostate cancer with obesity. Included to be transparent that human testing was attempted, not that human efficacy or safety was demonstrated.

• · Phase 1· First patient dosed 2012; no published completed efficacy/safety read-out; program discontinued

  Arrowhead Pharmaceuticals first-in-human Phase 1 study of Adipotide in obesity

  Separate industry-sponsored Phase 1 obesity programme. No NCT identifier confirmed here; clinical development subsequently stalled.

1. 01
   Reversal of obesity by targeted ablation of adipose tissue — Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W, Nature Medicine (2004)

   Landmark paper: in vivo phage display identifies the CKGGRAKDC/prohibitin homing motif and shows pro-apoptotic targeting reverses obesity in mice.

2. 02
   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)

   Pivotal non-human-primate study: ~11% weight loss over 28 days and improved insulin resistance, with a dose-dependent, reversible renal injury signal.

3. 03
   Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight — Kim DH, Woods SC, Seeley RJ, Diabetes (2010)

   Mechanistic rodent follow-up showing the adipose-endothelium pro-apoptotic peptide reduces body weight largely by reducing food intake.