Adipotide Research

Adipotide is a synthetic chimeric peptidomimetic investigated as a candidate obesity drug. Adipotide is a research chemical only, not approved for human therapeutic use and not for human consumption. Every efficacy finding comes from mice or monkeys, and the one registered human study was terminated at four participants and published nothing.

Molecular identity

The construct in the primary papers is CKGGRAKDC-GG-D(KLAKLAK)2 ^[2]. A nine-residue homing motif that binds prohibitin is joined by a glycine-glycine linker to a proapoptotic module built from D-amino acids ^[1][2]. That D-amino acid content is one reason adipotide is classed as a peptidomimetic rather than a natural peptide ^[2].

The public database entry gives CAS 859216-15-2, PubChem CID 163360068, formula C111H206N36O28S2 and molecular weight 2557.2 ^[7]. That record describes an idealized linear free acid ^[7]. It encodes neither the disulfide bond in the homing motif, nor the C-terminal amide, nor the D-stereochemistry the molecule's function depends on ^[7]. A certificate of analysis checked against it therefore proves less than it appears to.

The human record

The only registered human trial, NCT01262664, was a first-in-man phase 1 at MD Anderson Cancer Center ^[4]. It was single-arm, open-label and non-randomized, in men with metastatic prostate cancer and obesity, and it is filed under the development name Prohibitin-Targeting Peptide 1 ^[4]. Planned design was up to five dose levels of three participants each, and actual enrollment was four ^[4]. Co-primary endpoints covered an acceptable dose level and a body-weight change threshold at the end of dosing ^[4]. It ran from May 2012 to a January 2019 close-out, and the registry's entire stated reason is "Terminated per PI's request" ^[4]. No results section was posted and no publication exists ^[4].

Four people, in an advanced cancer population, with no reported outcome is the entire human evidence base. The absence of reported harm is not evidence of safety.

Vendor pages widely state that the trial stopped for dose-limiting nephrotoxicity and that development ended in 2019 over kidney damage. The registry supports neither statement, and no trial safety data has ever been released ^[4]. The 2019 date is a record close-out, not a finding ^[4]. Repeating that story would invent a human safety finding, and the real renal signal belongs to the monkeys ^[2].

Animal evidence

In vivo phage display isolated the CKGGRAKDC motif, which homes to white fat vasculature, and identified prohibitin as its binding partner ^[1]. Targeting a proapoptotic peptide to prohibitin ablated white adipose tissue and reversed established obesity in mice, with no detectable adverse effects reported ^[1]. That safety statement is a mouse observation, and it did not hold when the compound reached primates ^[2].

In obese rhesus macaques (n=15; 5 control, 10 treated), four weeks of daily subcutaneous dosing was followed by four weeks of recovery ^[2]. Treated animals lost 7.4% to 14.7% of pretreatment body weight against +1.0% to -3.5% in controls, and BMI fell 3.7% to 17.3% ^[2]. Body weight, BMI and abdominal circumference continued to fall for three weeks after dosing stopped ^[2]. Total body fat on DEXA fell by an average of 38.7% in treated animals ^[2]. It also fell 14.8% in the controls, which materially shrinks the placebo-adjusted effect ^[2]. Both figures come from a weekly-scanned subset, not all 15 animals ^[2]. Insulin AUC on intravenous glucose tolerance testing fell significantly (P = 0.019), and the insulinogenic index was significantly lowered (P = 0.006) ^[2].

Weight loss occurred concurrently with a reduction in food intake, and the authors conceded that mild nausea as a contributor could not be completely ruled out ^[2]. Lean rhesus monkeys at the lower dose levels did not lose weight at all, and metabolic rate could not be assessed ^[2].

A comment in the same journal argued the weight loss may instead reflect a direct effect of adipotide on food consumption ^[3]. The original investigators replied in the same issue ^[3]. The exchange is unresolved, and it is not a refutation.

The published counterweight used pair-fed mice, and reported that adipotide improved glucose tolerance rapidly and independently of weight loss and food intake ^[5]. Treatment lasted two to three days ^[5]. It does not address whether the primate weight loss was appetite-mediated, and it demonstrates nothing in humans ^[5].

In diet-induced obese mice, a prohibitin-targeted nanoparticle carrying the same proapoptotic payload reduced body weight at a low dose, whereas adipotide itself did not ^[6]. Only one low dose level of adipotide was tested, so this is a dose-specific null, not proof of inactivity ^[6]. The authors were advancing the competing nanoparticle platform against which adipotide was the benchmark ^[6].

Renal findings in primates

Above the lowest level tested, serum creatinine rose in a slight-to-moderate, dose-dependent way, without a concurrent rise in blood urea nitrogen ^[2]. Serum phosphorus and potassium showed mild-to-moderate, time- and dose-dependent falls, and mild dehydration appeared at the highest dose levels ^[2]. Urinalysis showed mild-to-marked glucosuria, mild-to-moderate proteinuria, increased urine volume, and a slight-to-mild rise in transitional and renal epithelial cells ^[2].

The authors read this as altered proximal tubular function with tubular injury ^[2]. Creatinine rising without a matching BUN rise led them to consider altered tubular handling of creatinine ^[2]. The change is therefore not cleanly readable as a fall in glomerular filtration rate ^[2].

A GLP 28-day study in lean rhesus monkeys used 20 animals: 15 dosed across three levels and 5 controls ^[2]. Animals necropsied 24 hours after the final dose showed dose-dependent kidney lesions absent in controls ^[2]. Lesions were minimal to mild in the low-dose group and in most of the middle-dose monkeys, and minimal to moderate at the high dose ^[2]. They were classified as degenerative or necrotic, including single-cell necrosis, and as reactive or regenerative ^[2].

Most serum and urine changes reversed within 28 days of stopping, and lesions in the recovery-necropsy animals were minimal ^[2]. The authors' own summary characterizes the injury as relatively mild, predictable and reversible ^[2]. That characterization should be attributed to them rather than asserted here as established fact. Minimal tubular degeneration remained at the end of recovery in one middle-dose and two high-dose monkeys ^[2]. One treated monkey in each efficacy study still had slightly raised serum creatinine and glucosuria ^[2]. Largely reversible with residual changes in a minority of animals is accurate, and fully reversible overstates the record.

Human renal safety is unknown, because four people were dosed and nothing was published ^[4].

Pharmacokinetics

No pharmacokinetic data have been published for adipotide, in any species ^[8]. A PubMed search returns seven records, of which four concern the compound, and all four are animal work or commentary ^[8]. None reports a half-life, a bioavailability figure or clearance data, and the primate paper contains none either ^[2][8]. Every published study used subcutaneous administration, and no oral study appears ^[2][8]. This is a bounded absence-of-publication claim ^[8].

Regulatory and anti-doping status

Field-qualified openFDA queries against the label database and Drugs@FDA return no record and no approved application for Adipotide ^[9]. EU regulatory status could not be verified from the sources used here, so no claim is made either way. Absence of approval is not a safety finding ^[9].

Adipotide is not named on the 2026 WADA Prohibited List ^[10]. Not named does not mean permitted. Section S0 reaches substances not approved for human therapeutic use, expressly including drugs in development and discontinued drugs ^[10]. Adipotide is a discontinued investigational compound, and no approval for it was found in the records checked here ^[9]. Athletes must seek a binding determination from their own anti-doping organization, and nothing here is clearance.

Conflicts of interest in the literature

The compound's inventors hold patents on adipotide with royalty entitlement contingent on commercial success ^[2]. Two were paid consultants to the company developing it, and they, their institution and a further author held equity in it ^[2]. One author listed that company as an institutional affiliation ^[2]. The sponsor-affiliated team both generated the primate toxicity data and characterized it as mild and reversible ^[2]. The single human trial was sponsored by the institution holding the patents, and the primate work also carried NIH funding ^[4][2].

References

1. 1

   Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004. PMID 15133506. DOI: 10.1038/nm1048
2. 2

   Barnhart KF, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011. PMID 22072637. DOI: 10.1126/scitranslmed.3002621
3. 3

   Criscione L. Comment on "A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys". Sci Transl Med. 2012;4(131):131le2, with author reply at 131lr2. PMID 22539771. DOI: 10.1126/scitranslmed.3003760
4. 4

   M.D. Anderson Cancer Center. A First-in-Man, Phase I Evaluation of a Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity. ClinicalTrials.gov NCT01262664. Registry record only; terminated, enrollment 4, no results posted.
5. 5

   Kim DH, et al. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012. PMID 22733798. DOI: 10.2337/db11-1579 (pair-fed mouse glucose-tolerance study; the Methods specify CKGGRAKDC-GG-D(KLAKLAK)2, i.e. adipotide, which the paper calls the proapoptotic peptide)
6. 6

   Hossen N, et al. A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release. 2013. PMID 23871959. DOI: 10.1016/j.jconrel.2013.07.013 (nanoparticle comparison in diet-induced obese mice, with adipotide as the bioconjugate comparator)
7. 7

   PubChem Compound record CID 163360068; CAS 859216-15-2. NCBI PubChem PUG-REST, CAS string round-tripped to the CID and re-verified 2026-08-28: C111H206N36O28S2, 2557.2. Formula and molecular weight represent an idealized linear free acid.
8. 8

   NCBI PubMed literature sweep. E-utilities esearch, term "adipotide", re-run 2026-08-28. Seven records returned (PMIDs 22072637, 22539771, 22733798, 23871959, 27862873, 30785999, 31996464); the last three concern metformin and GLP-1, epigenetic age acceleration, and a GPER agonist, not adipotide. No record reports pharmacokinetic data, and none reports a human outcome. Scope: PubMed only.
9. 9

   US Food and Drug Administration. openFDA drug/label and drug/drugsfda APIs, field-qualified substance-name queries; data snapshot 2026-08-26. No record and no approved application for adipotide.
10. 10

    World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026, in force 1 January 2026. Adipotide not named; Section S0 applies to non-approved substances.