Adipotide

Adipotide is two functional halves joined together. The CKGGRAKDC sequence binds prohibitin, a protein that is unusually abundant on the surface of endothelial cells lining white adipose tissue capillaries. The D(KLAKLAK)2 domain is a well-characterised pro-apoptotic amphipathic peptide that disrupts mitochondrial membranes once internalised. Together they selectively ablate adipose vasculature, causing the fat tissue to involute from lack of perfusion. In obese rhesus monkeys this produced roughly 11% body weight loss in four weeks with improved insulin sensitivity. It also produced dose-dependent renal proximal tubule damage, because the kidney concentrates and reabsorbs the peptide. That toxicity, not efficacy, is why adipotide never reached meaningful human development.

Targets: Prohibitin, Annexin A2, Mitochondrial membrane

• · Primate work used weight-scaled daily dosing (around 0.43 mg/kg/day) for four weeks. Grey-market protocols circulating at fixed milligram doses are not derived from any human study, and there is no human dose-finding data to anchor them to.

Work out your exact syringe units →

• very commonRenal proximal tubule injury— Dose-dependent and the reason the compound was abandoned. This is the defining risk, not a footnote.
• commonDehydration and reduced food and water intake— Observed in primate studies.
• commonInjection-site reaction

• Any pre-existing kidney disease or reduced eGFR - this compound targets the organ that is most likely to be damaged.
• Dehydration or use of other nephrotoxic drugs (NSAIDs, aminoglycosides, contrast).
• Pregnancy.
• Honestly: there is no human population in which the risk-benefit for this compound has been shown to be acceptable.

• cautionsemaglutide — GLP-1-induced vomiting and dehydration would compound adipotide's renal risk considerably.

• · Serum creatinine and eGFR - frequently, if at all used.
• · Urinalysis for proteinuria and tubular casts.
• · Hydration status.

Never approved; development effectively abandoned. Sold as a research chemical.

• Barnhart et al. 2011, a peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys, Science Translational Medicine (preclinical)
• Kolonin et al. 2004, reversal of obesity by targeted ablation of adipose tissue, Nature Medicine (preclinical)

Adipotide is not a metabolic drug at all - it is a targeted cytotoxic, borrowed from cancer vascular-targeting research, aimed at fat instead of tumours. The homing peptide binds prohibitin, a protein that is unusually abundant on the endothelial surface of white adipose tissue vasculature. Once the conjugate is anchored there, it is internalised and the D(KLAKLAK)2 domain disrupts mitochondrial membranes, triggering apoptosis in the endothelial cell. Kill the blood supply and the adipocytes it feeds die of ischaemia. In obese rhesus monkeys this produced substantial fat loss with improved insulin sensitivity, and the effect was fast - fat mass fell within two to four weeks. It also produced dose-dependent renal proximal tubule damage, because the kidney concentrates the peptide and the killing domain does not care what cell it is in once it gets there. That toxicity is intrinsic to the design rather than an impurity or a formulation problem, and it is why the programme did not continue. A single small phase 1 trial in obese men with prostate cancer was conducted and did not lead anywhere. What is sold to consumers as adipotide today is a research chemical with no human efficacy data, a documented organ-toxicity mechanism in primates, and no way to monitor for the specific injury it causes until creatinine has already risen - by which point proximal tubular damage has occurred. Of everything in this class, this is the compound where the gap between the marketing story and the evidence is widest.

Kidneys. The mechanism that kills adipose vasculature also kills renal proximal tubular cells, because the kidney concentrates the peptide and the pro-apoptotic domain has no intrinsic selectivity. In the primate study this was dose-dependent and it is what ended the programme. It is not an impurity problem that better sourcing solves, and it is not a dose problem that lower dosing reliably solves - it is what the molecule does. There is essentially no human efficacy data. And the injury is silent until it is not: proximal tubular damage precedes any rise in creatinine, so someone monitoring only creatinine will find out late.

• Prohibitin (PHB) on white adipose tissue vascular endothelium — The CKGGRAKDC homing sequence was selected by phage display for adipose vasculature binding; specific affinity not verified

  Anchors the conjugate to adipose-supplying endothelium and drives internalisation. This is the targeting half of the molecule and it is genuinely selective for white fat vasculature.

• Mitochondrial membranes (not a receptor) — Not applicable

  The D(KLAKLAK)2 domain disrupts mitochondrial membrane integrity, triggering apoptosis. It has no selectivity of its own - all the selectivity comes from the homing peptide, which is why the renal proximal tubule, where the peptide concentrates, is damaged.

• Adipotide in obese rhesus monkeys Preclinical (non-human primate) · 4 weeks · 2011

  Substantial reduction in fat mass with improved insulin resistance, accompanied by dose-dependent renal proximal tubule injury.

Fat mass reductions appeared within two to four weeks in primate studies. Renal injury appeared on the same timescale. There is no human timeline because there is essentially no human data.

There is nothing sensible to say about stacking a nephrotoxic experimental cytotoxic with anything. If someone is using it despite that, the interactions that matter are anything else that stresses the proximal tubule: NSAIDs, aminoglycosides, contrast media, high-dose vitamin C, dehydration, and any of the incretins during a period of vomiting. Adding a GLP-1 agonist and then getting dehydrated from vomiting while running adipotide is a genuinely dangerous combination.

Against everything else in this class: adipotide is the only compound here that works by killing tissue rather than by signalling, and it is the only one with a documented organ-toxicity mechanism that terminated its own development. Compared with an approved incretin, the risk-to-evidence ratio is not in the same universe - tirzepatide has 20.9% weight loss in 2,539 people over 72 weeks, and adipotide has fat loss in monkeys plus nephrotoxicity in the same monkeys. There is no argument for choosing it.

$60–$250/month. Research chemical pricing. Market observation, not verified pricing.

• ?No human pharmacokinetic or efficacy data exists in the public domain.
• ?The sequence designation CKGGRAKDC-GG-D(KLAKLAK)2 is as published in the peptide-targeting literature and was not verified against a primary structural source in this session.
• ?The single phase 1 trial in obese men with prostate cancer was not located and verified in this session; its results are not characterised here.
• ?Whether the nephrotoxicity is avoidable at any dose that produces fat loss has never been established, and the programme was stopped rather than answering the question.
• ?Cost figures are market observations, not verified pricing.

• A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys Barnhart KF et al., Sci Transl Med, 2011 · PMID 22072637

  The primate study. Read the renal findings, not just the weight findings - both are in the same paper, and the toxicity is the reason there is no drug.