Adipotide

Adipotide is an engineered peptide designed to destroy the blood vessels feeding white fat tissue, causing fat loss without a measured change in food intake — it works by joining a fat-tissue 'homing' sequence to a cell-killing sequence. It showed this effect in mice and, in a monkey study, in obese primates too, but that same monkey study found dose-limiting kidney toxicity, a serious safety signal. It is not FDA-approved; a small early human safety trial was started but terminated early with no results ever published, and outside research it's available only through unregulated supply chains.

Adipotide was studied as a fat-loss compound designed to cut off the blood supply to fat tissue. In a 2004 mouse study it reduced body weight and fat mass without a measured change in food intake, and a 2011 study extended this to obese monkeys — but that study documented dose-limiting kidney toxicity as the main adverse event, a serious safety signal. A first-in-human Phase 1 trial was started but terminated early after only a handful of patients, with no published data, so there is no published human evidence.

Not FDA-approved for any indication. A first-in-human Phase 1 trial (NCT01262664, MD Anderson, "Prohibitin-TP01") was conducted but terminated in 2019 after enrolling only 4 of a planned up-to-39 patients; no results were ever published. The published evidence base is otherwise exclusively preclinical: foundational mouse work (Kolonin 2004 Nature Medicine) plus the rhesus monkey study (Barnhart 2011 Science Translational Medicine). Documented renal proximal tubule toxicity in the rhesus monkey study as the dose-limiting adverse event — the widely-cited reason the human program was abandoned. Available exclusively as a research compound through unregulated research-supply chains; given the renal toxicity signal and absence of published human trial data, research-community use is sparse compared to the GLP-1 ra family or peptide-axis library entries. Not DEA-scheduled. WADA status: not explicitly named on the 2026 Prohibited List as of last review (the S0 "Non-Approved Substances" catch-all likely captures a discontinued/non-approved drug like adipotide).

Adipotide is not FDA-approved and produced no published human trial results (a first-in-human Phase 1 trial was terminated early), and animal studies documented dose-limiting kidney toxicity, so its safety in people is unknown and potentially serious. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Adipotide is not FDA-approved for any indication; a first-in-human Phase 1 trial (NCT01262664) was terminated at n=4 with no published results. The published evidence base is otherwise exclusively preclinical (mouse + rhesus monkey). Adipotide is available exclusively as a research compound through unregulated research-supply chains. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ The Barnhart 2011 Science Translational Medicine rhesus monkey study documented renal proximal tubule toxicity as the dose-limiting adverse event. This is the most concerning safety signal in the adipotide preclinical literature. The renal toxicity finding is the dominant reason research-community use of adipotide is sparse compared to other body-composition compounds in the library — researchers extrapolating from the primate safety signal generally choose other compounds (GLP-1 ra family, the metabolic-modulator small molecules AICAR / 5-amino-1MQ) with substantially better-characterized safety profiles. The renal toxicity is mechanistically plausible given the D[KLAKLAK]2 domain's pro-apoptotic activity in any tissue with sufficient peptide exposure plus the renal proximal tubule's high-density mitochondrial content.

⚠️ Adipotide is a chimeric pro-apoptotic peptide that selectively ablates adipose-tissue vasculature — mechanistically distinct from anything else in the Vialwise library. Unlike the metabolic modulators (AICAR, 5-amino-1MQ) that operate on cellular energy-balance pathways, or the GLP-1 ra family that suppresses appetite, adipotide produces fat loss via direct cytotoxic destruction of white adipose tissue vasculature. The homing peptide CKGGRAKDC binds prohibitin on adipose endothelium; the fused D[KLAKLAK]2 amphipathic peptide disrupts mitochondrial membranes in endothelial cells; adipose vasculature is ablated; downstream adipose tissue regresses. This is a fundamentally different therapeutic concept from any other entry in the library — body composition change without food-intake reduction, mediated by tissue ablation rather than metabolic regulation.

⚠️ The published evidence base is exclusively preclinical (mouse + rhesus monkey) — the one human trial produced NO published results. Foundational mouse work was published in 2004 (Kolonin Nature Medicine);[¹] follow-on rhesus monkey work was published in 2011 (Barnhart Science Translational Medicine).[²] A first-in-human Phase 1 trial (NCT01262664, MD Anderson) was conducted but terminated in 2019 after enrolling only 4 of a planned up-to-39 patients, with no results ever published[⁴] — the renal toxicity signal in the primate study plus the cytotoxic mechanism are the widely-cited reasons the program was abandoned. Research-community use of adipotide in humans operates on the substantial preclinical-to-clinical translation gap plus the documented primate renal-toxicity signal plus a terminated human trial — qualitatively different evidence base from the GLP-1 ra family or even other preclinical entries (AICAR has decades of acadesine CABG trial data; 5-amino-1MQ has only mouse data but lacks the primate toxicity signal).

Based on articles retrieved from PubMed-indexed research, adipotide is an engineered chimeric peptidomimetic developed by the Arap/Pasqualini laboratory at MD Anderson Cancer Center as part of the broader vascular-targeting "homing peptide" research program.[¹] The full sequence CKGGRAKDC-GG-D[KLAKLAK]2 combines two functionally-distinct domains: (a) the CKGGRAKDC homing-peptide domain — a 9-amino-acid sequence identified via in vivo phage-display screening that selectively binds prohibitin on the vasculature of white adipose tissue; (b) the D[KLAKLAK]2 pro-apoptotic domain — a 14-amino-acid amphipathic α-helical peptide composed of D-stereoisomer residues that disrupts mitochondrial membranes when delivered intracellularly, inducing rapid apoptosis. The two domains are joined by a glycine-glycine linker. The combined chimeric architecture localizes pro-apoptotic activity specifically to adipose endothelium — producing selective ablation of white adipose tissue vasculature with downstream adipose tissue regression.

Mechanism. Adipotide's mechanism operates in three steps: (1) Systemic administration → plasma circulation → binding of the CKGGRAKDC domain to prohibitin on white adipose tissue vasculature; (2) Internalization of the chimeric peptide into adipose endothelial cells via prohibitin-mediated endocytosis; (3) Release of the D[KLAKLAK]2 domain into the cytosol → disruption of mitochondrial membranes → endothelial cell apoptosis → adipose vasculature ablation → adipose tissue regression. Critically, the mechanism is reported to produce body composition change without a measured change in food intake — the Kolonin 2004 mouse study and Barnhart 2011 rhesus study both documented this finding,[¹][²] though a published peer-reviewed Comment (Criscione 2012, with author reply) argued the observed weight loss could partly reflect a direct effect of adipotide on food consumption rather than pure vascular ablation — i.e., the mechanism-vs-appetite question is contested in the literature, not settled.[⁵]

Foundational mouse work (Kolonin 2004 Nature Medicine).[¹] The Kolonin 2004 publication from the Arap/Pasqualini group at MD Anderson is the foundational adipotide publication. Obese mice received systemic adipotide administration; the study demonstrated prohibitin localization to white adipose vasculature, selective ablation of adipose endothelium, reduction in body weight and adipose mass, and reversal of obesity-related metabolic markers — without changes in food intake. The study established the homing-peptide-plus-pro-apoptotic-peptide chimeric concept as a viable therapeutic approach for adipose tissue regression.

Rhesus monkey work (Barnhart 2011 Science Translational Medicine).[²] The Barnhart 2011 publication from the Arap/Pasqualini group extended the work to obese rhesus monkeys — the primate model that would anchor any human translational program. Daily SC adipotide dosing over 4-week cycles produced measurable reductions in body weight and adipose mass in obese rhesus monkeys, with body composition changes consistent with the preceding mouse data. Critically, the rhesus study documented the dose-limiting adverse event: renal proximal tubule toxicity. The renal toxicity was the primary safety concern and is mechanistically attributable to the D[KLAKLAK]2 domain's pro-apoptotic activity in renal proximal tubule cells (which have high mitochondrial density and are exposed to the systemic peptide via glomerular filtration and tubular reabsorption). This renal toxicity finding has been the dominant barrier to clinical translation — a first-in-human Phase 1 trial (NCT01262664, MD Anderson) was conducted but terminated in 2019 at n=4, and the program was subsequently abandoned with no results ever published.[⁴]

Regulatory status (US — current). Adipotide is not FDA-approved for any indication. An FDA-cleared first-in-human Phase 1 trial (NCT01262664, MD Anderson) was conducted but terminated at n=4, and no results were ever published.[⁴] The compound is available exclusively as a research compound through unregulated research-supply chains; not legally compoundable through US 503A pharmacies. Not DEA-scheduled.

Regulatory status (sport — WADA). Adipotide is not explicitly named on the 2026 WADA Prohibited List as of last review. However, the S0 "Non-Approved Substances" catch-all — which prohibits at all times any pharmacological substance not currently approved for human therapeutic use — likely captures a discontinued/non-approved drug like adipotide. The broader "cytotoxic adipose-targeting peptide" class is not currently a named WADA category. Users in regulated sport should verify the current WADA status directly via the WADA Prohibited List and their National Anti-Doping Organization before any use.

Common research interests. Despite the absent human clinical-trial evidence base and documented primate renal toxicity, adipotide is used in research-community contexts for: - Putative selective fat-loss effects — the dominant research-community use case, extrapolating from the Kolonin 2004 and Barnhart 2011 preclinical data.[¹][²] Research-community use is substantially sparser than for the GLP-1 ra family, AICAR, or 5-amino-1MQ given the documented primate renal toxicity signal. - Putative spot-reduction fat-loss effects — research-community use case extrapolating from adipotide's mechanism (selective adipose-vasculature targeting). Published evidence does not support tissue-specific spot reduction in human use. - Combined with other body-composition compounds — combined research-community use with GLP-1 ra family or metabolic modulators is reported but is not supported by published evidence and may compound the renal-toxicity risk.

Commonly reported

• Mild injection-site reactions — typical of SC injection
• Subjective fatigue or malaise — reported in research-community use; not well-characterized
• Mild GI symptoms — uncommon
• Subjective body-composition changes — the intended effect; reported in research-community use; not characterized in published human evidence
• The published primate evidence base documents renal proximal tubule toxicity as the dose-limiting adverse event.[²] This is the most concerning safety signal of any compound in the Vialwise library. Human use without rigorous renal function monitoring is high-risk.
• The mechanism (cytotoxic pro-apoptotic peptide) is fundamentally different from any other library entry — most library entries are receptor-binding agonists/antagonists or metabolic modulators that produce reversible pharmacological effects. Adipotide's mechanism is destructive (apoptosis of target endothelium); off-target tissue damage may be similarly irreversible.
• Long-term safety in humans is essentially unknown. No published human evidence exists. The primate safety signal alone warrants caution.

Serious

• Signs of acute kidney injury (decreased urine output, flank pain, edema, sudden weight gain from fluid retention) — given the documented primate renal proximal tubule toxicity, any indication of renal symptoms warrants immediate discontinuation and medical evaluation[²]
• Proteinuria, microscopic hematuria, or other proximal tubule injury markers on urinalysis — warrants immediate discontinuation and nephrology evaluation
• Severe allergic / hypersensitivity reaction — extremely rare but warrants immediate medical evaluation
• New cardiovascular symptoms — given the cytotoxic mechanism, off-target effects on other high-mitochondrial-density tissues (cardiac, hepatic) are theoretically possible; new-onset cardiovascular symptoms warrant medical evaluation

Active or recent renal disease — contraindicated given the documented primate renal proximal tubule toxicity[²]

Reduced baseline eGFR (<60 mL/min/1.73 m²) — contraindicated

Concurrent nephrotoxic medications (NSAIDs, aminoglycosides, IV contrast) — strongly contraindicated

Pregnancy and lactation — no human data; default to contraindicated

Pediatric use — no clinical-trial evidence base; default to contraindicated

Active malignancy — caution; cytotoxic mechanism may have unpredictable effects

History of mitochondrial disease — caution given the D[KLAKLAK]2 mitochondrial-disrupting mechanism

Severe cardiovascular disease — caution given the cytotoxic mechanism's theoretical off-target effects

Regulatory note (US): Adipotide is not FDA-approved for any indication and is not legally compoundable through US 503A pharmacies.

Regulatory note (sport): Not explicitly named on the 2026 WADA Prohibited List as of last review. Verify directly.

Not DEA-scheduled.

Critical: The Barnhart 2011 rhesus monkey study documented renal proximal tubule toxicity as the dose-limiting adverse event.[²] The one first-in-human Phase 1 trial (NCT01262664) was terminated at n=4 with no published results.[⁴] Research-community use without rigorous renal function monitoring is high-risk.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Apoptosis

Programmed cell death; a controlled process by which a cell self- destructs.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

1. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. (2004). Reversal of obesity by targeted ablation of adipose tissue. Nature Medicine, 10(6):625–632 (June 2004; published online May 9, 2004).(PMID 15133506)
2. Barnhart KF, Christianson DR, Hanley PW, Driessen WHP, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. (2011). A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Science Translational Medicine, 3(108):108ra112 (November 9, 2011).(PMID 22072637)
3. Arap W, Pasqualini R, et al. Broader homing-peptide / vascular-targeting research program at MD Anderson Cancer Center, 1998 onward. The adipotide construct emerged from the Arap/Pasqualini in vivo phage-display research program that identified tissue-specific endothelial markers via peptide-library screening in living animals. The CKGGRAKDC homing peptide was originally identified as a prohibitin-binding sequence specific to white adipose tissue vasculature. The D[KLAKLAK]2 pro-apoptotic peptide had been previously developed as a stand-alone amphipathic α-helical mitochondrial-disrupting agent (Ellerby et al., several earlier publications). Source for: the broader homing-peptide / vascular-targeting research context; the CKGGRAKDC peptide discovery via in vivo phage display; the D[KLAKLAK]2 pro-apoptotic peptide history; the rationale for the chimeric architecture.

• Follistatin — same mechanism class
• FOXO4-DRI — same mechanism class
• PNC-27 — same mechanism class
• Tesofensine — same mechanism class
• Amycretin — shared research area
• AOD-9604 — shared research area