Adipotide
Prohibitin-Targeting Peptide 1 (FTPP)
Adipotide (FTPP) is a chimeric peptidomimetic that induces targeted apoptosis of white adipose tissue vasculature via cell-surface prohibitin, producing 10.6% body weight loss and 38.7% fat mass reduction in obese rhesus macaques (PMID 22072637). A Phase 1 trial (NCT01262664) was terminated in 2019 without published results. Dose-limiting renal proximal tubule toxicity and a published food-intake confound critique (PMID 22539771) are major caveats.
Last updated: 2026-03-09
Safety Summary
The primary and dose-limiting toxicity in primate studies was renal proximal tubule dysfunction consistent with Fanconi-like syndrome, characterized by elevated serum creatinine, proteinuria, glucosuria, and electrolyte abnormalities (PMID 22072637). Effects were dose-dependent and described as partially reversible upon cessation of treatment. A later study using the CKGGRAKDC sequence as a liposomal ligand found elevated kidney uptake with ATS-targeted nanoparticles, providing mechanistic support for kidney-specific accumulation of the targeting domain (PMID 31725756). Renal toxicity was consistent across all primate species tested (rhesus macaques, baboons, cynomolgus monkeys). In a related D(KLAKLAK)2-containing compound (BMTP-78), renal toxicity was similarly observed as a class effect, alongside unexpected fatal cardiac arrhythmias at higher doses that were unique to BMTP-78 and not seen with adipotide (PMID 29205207). No human adverse event data has been published from NCT01262664.
Known Side Effects
Observed in all treated primate cohorts at efficacious doses; human frequency not established
Dose-dependent in nonhuman primates; human frequency not established
Observed in treated nonhuman primates; human frequency not established
Observed in treated nonhuman primates; human frequency not established
Observed in treated nonhuman primates; human frequency not established
Who Should NOT Use This
Dose-limiting renal proximal tubule dysfunction was the primary toxicity across all primate species tested (PMID 22072637). ATS-targeted liposomes showed elevated kidney uptake independent of payload delivery to adipose tissue (PMID 31725756), suggesting the nephrotoxicity liability is intrinsic to the CKGGRAKDC targeting approach.
Given the established renal toxicity profile in primates (PMID 22072637), concurrent use with other nephrotoxic agents (NSAIDs, aminoglycosides, contrast dye) would be expected to increase risk of renal injury. This is extrapolated; no human drug interaction data exists.
Talk to Your Doctor
Before considering Adipotide, discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-14]
Evidence Assessment
Tier 4 (Phase 1 or limited human data, strong preclinical). A Phase 1 dose-escalation trial (NCT01262664) was initiated in 2012 in castration-resistant prostate cancer patients but terminated in January 2019 without publishing any results (PMID 40760703). No evaluable human efficacy or safety data exists. The preclinical evidence includes multi-species primate studies (rhesus macaques, baboons, cynomolgus monkeys) with quantified outcomes (PMID 22072637), and human target validation via in vivo phage-display in cancer patients (PMID 22049339). Critical caveats: (1) nearly all primary preclinical data originates from a single research group (Kolonin, Arap, Pasqualini et al.); (2) independent replication of the key primate efficacy findings has not been published; (3) a published critique raised the food intake confound as an alternative explanation for efficacy (PMID 22539771); (4) no human pharmacokinetic or adverse event data has been published.
1Reversal of obesity by targeted ablation of adipose tissuePMID 15133506
Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W - Nature Medicine (2004) - animal study - Multiple cohorts of obese (ob/ob) and lean mice
Proof-of-concept demonstrating that subcutaneous administration of FTPP in obese mice caused approximately 30% weight loss over 28 days through targeted apoptosis of WAT vasculature. Identified CKGGRAKDC as the homing sequence for WAT vasculature via in vivo phage-display selection. Established the chimeric bipartite design and D-enantiomer protease resistance.
Limitations: Mouse model only. Single research group (MD Anderson). Dose-response and toxicity not fully characterized.
2A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeysPMID 22072637
Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG et al. - Science Translational Medicine (2011) - animal study - Multiple primate cohorts including fixed-dose study (n=15; 5 controls, 10 treated rhesus macaques) plus dose-finding cohorts in baboons and cynomolgus macaques
Primary non-human primate efficacy and toxicity study. At 0.43 mg/kg daily SC for 28 days: 10.6% mean body weight reduction, 38.7% total body fat reduction (DEXA), 17.5% abdominal WAT reduction by MRI (increasing to 27.0% at 4-week recovery). Significant insulin sensitivity improvement (reduced insulin AUC). Dose-dependent renal proximal tubule dysfunction was the primary dose-limiting toxicity.
Limitations: Single research group (MD Anderson/UT Southwestern). No independent replication published. A published critique (PMID 22539771) argued food intake reduction could explain the weight loss results.
3Comment on 'A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys'PMID 22539771
Criscione L - Science Translational Medicine (2012) - letter/comment - N/A (commentary)
Published comment arguing that reduced food intake may account for much of the reported weight loss in the Barnhart 2011 primate study, questioning whether selective adipose vascular ablation alone explains the results. An author response was also published (DOI 10.1126/scitranslmed.3004103).
Limitations: Commentary without new experimental data.
4Vascular ligand-receptor mapping by direct combinatorial selection in cancer patientsPMID 22049339
Staquicini FI, Cardo-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN et al. - Proceedings of the National Academy of Sciences (2011) - translational research (human vascular mapping) - Cancer patients (in vivo phage-display selection)
Confirmed that prohibitin and annexin A2 (ANXA2) are expressed in the vasculature of human white adipose tissue using in vivo combinatorial phage-display selection in living cancer patients. Validates these proteins as molecular targets in human tissue.
Limitations: Confirmed target expression, not adipotide activity. Cancer patient population may not represent obesity indication.
5Prohibitin Ligands in Cell Death and Survival: Mode of Action and Therapeutic PotentialPMID 23521790
Thuaud F et al. - Chemistry and Biology (2013) - review - N/A (review)
Comprehensive review of prohibitin biology and PHB ligands. Describes adipotide as CKGGRAKDC-GG-D(KLAKLAK)2, summarizes a 28% body-fat reduction in obese primates, and confirms adipotide had entered Phase I by July 2012. Provides extensive context on prohibitin's roles in cell survival, metabolism, inflammation, and the Ras-C-Raf-MEK-ERK pathway.
Limitations: Review article; no primary adipotide data. The 28% figure differs from the primary paper's 38.7% (PMID 22072637), likely reflecting different calculation methods.
6A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medicationPMID 23871959
Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H - Journal of Controlled Release (2013) - animal study - Diet-induced obese mice
Compared prohibitin-targeted nanoparticles (PTNP) encapsulating the KLA proapoptotic peptide versus adipotide (bioconjugate) in diet-induced obese mice. KLA-PTNP produced greater reduction in body weight and ectopic fat than adipotide, with improved adiponectin levels and no hepatotoxicity. Demonstrates an alternative delivery approach using the same targeting principle.
Limitations: Mouse model. Different delivery system than clinical adipotide. Single research group.
7Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissuePMID 27468426
Not fully specified in available data - JCI Insight (2016) - original research - Mouse and human adipose tissue samples
Demonstrated that prohibitin and annexin A2 co-localize on the luminal surface of WAT endothelial cells and together regulate fatty acid transport into adipose tissue. Provides the molecular basis for adipotide targeting specificity.
Limitations: Primarily mechanistic; does not address therapeutic efficacy or safety.
8Importance of thorough tissue and cellular level characterization of targeted drugs in the evaluation of pharmacodynamic effectsPMID 31725756
Bauknight DK et al. - PLoS ONE (2019) - animal study (biodistribution) - Leptin-deficient obese mice (ob/ob), n=6 per group in key experiments
ATS (CKGGRAKDC)-conjugated liposomes did not significantly increase adipose tissue uptake relative to untargeted liposomes but did significantly increase kidney uptake. Most liposome uptake in adipose tissue was by macrophages via phagocytosis rather than prohibitin-specific endothelial targeting. Challenges the assumption that ATS provides adipose-selective delivery.
Limitations: Evaluated the targeting sequence on a liposomal carrier rather than the bare adipotide peptide conjugate. Mouse model (ob/ob). Different delivery platform from clinical adipotide.
9Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity developmentPMID 25342467
Daquinag AC et al. - Cell Death and Differentiation (2014) - animal study - Diet-induced obese C57BL/6 mice
Describes D-WAT (dWAT7-KLAKLAK2), a related but chemically distinct hunter-killer peptide targeting white adipocyte progenitors via delta-decorin receptor. D-WAT promotes beige adipocyte differentiation and suppresses obesity long-term. The paper explicitly contrasts D-WAT with adipotide: adipotide induces acute but relapsing obesity reversal through vascular ablation, while D-WAT produces long-term WAT growth suppression through progenitor depletion.
Limitations: D-WAT is NOT adipotide -- different targeting sequence (WAT7 vs CKGGRAKDC) and different target receptor (delta-decorin vs prohibitin). The beige differentiation finding applies to D-WAT, not adipotide. Mouse model. Single research group.
10Phase 1 Study of Adipotide in Patients With Castration-Resistant Prostate CancerNCT01262664
Logothetis CJ (PI); Arrowhead Pharmaceuticals / MD Anderson Cancer Center - ClinicalTrials.gov (2012) - clinical trial (Phase 1) - Not disclosed (dose-escalation design)
Phase 1 dose-escalation safety study. Trial terminated 18 January 2019 per principal investigator request (PMID 40760703). No efficacy, safety, or pharmacokinetic results have been published as of March 2026.
Limitations: Terminated without publication of results. Cancer patient population, not obesity. Unknown sample size, doses, and outcomes.
11Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma: preclinical efficacyPMID 29205207
Not fully specified in available data - Not specified in available data (2017) - preclinical / GLP toxicology - Multiple cohorts of rodents and nonhuman primates
GLP toxicology studies for BMTP-78, a related D(KLAKLAK)2-containing compound. Renal toxicity was the primary finding across species, similar to adipotide (class effect). Provides PK reference data for BMTP-11 (plasma half-life 0.67-0.89h in cynomolgus monkeys). Confirms that both adipotide (NCT01262664) and BMTP-11 (NCT00872157) received FDA IND clearance.
Limitations: BMTP-78 and BMTP-11 are NOT adipotide -- different targeting domains. Cardiac toxicity unique to BMTP-78 was not seen with adipotide. Used as class-effect reference only.
12Systems Biology Will Direct Vascular-Targeted Therapy for ObesityPMID 32760294
Not fully specified in available data - Frontiers in Physiology (2020) - review - N/A (review)
Reviews vascular-targeted obesity therapy including adipotide. Discusses ischemia mechanism of WAT regression and proposes systems biology approaches to identify future therapeutic windows avoiding renal toxicity.
Limitations: Review article; no primary data.
13Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition EraPMID 37894644
Not fully specified in available data - Not fully specified in available data (2023) - review - N/A (review)
Confirms adipotide sequence, prohibitin targeting mechanism, consistent WAT reduction across three monkey species, and states the first human clinical trial was discontinued in 2019.
Limitations: Review article. Brief mention in broader therapeutic peptide context.
14Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)PMID 40760703
Not fully specified in available data - Not fully specified in available data (2025) - review - N/A (review)
Pipeline table lists adipotide as a PHB1-targeting Phase I program, gives NCT01262664, and marks program as discontinued 18 January 2019. Provides patent information. Developer: Arrowhead Pharmaceuticals (subsidiary Ablaris Therapeutics).
Limitations: Review article. Adipotide discussed briefly in broader adipose-targeting review.