Peptide profile
Adipotide (FTTP)
Targeted fat-depot destruction via vascular apoptosis · also known as FTTP, Pro-Gly-Trp-Leu-Ala-Glu-Gly-Trp-Gly-Gly-Cys-NH2 (D[KLAKLAK]2), Prohibitin-targeting peptide
Compare Adipotide (FTTP) with other peptides →Summary
Adipotide (also called FTTP) is an experimental peptidomimetic compound designed to selectively destroy the blood supply to white adipose tissue by targeting prohibitin, a protein highly expressed on the vasculature feeding fat cells. Originally developed at MD Anderson Cancer Center, it demonstrated dramatic fat loss in obese rhesus monkeys without dietary restriction. It remains a research compound with no approved human clinical use.
- Typical dose
- ~1–2 mcg/kg/day (based on rhesus monkey research; no validated human dose established)
- Half-life
- ~unknown; estimated short (~1-2 hours based on peptide class)
- Route
- Subcutaneous
- Cycle length
- 4 weeks (based on animal study protocol; human cycle length unknown)
Mechanism
How it works
Adipotide is a chimeric peptide containing two functional domains: a targeting sequence (CKGGRAKDC) that homes to prohibitin expressed on the luminal surface of blood vessels feeding white adipose tissue, and a pro-apoptotic domain (D[KLAKLAK]2) that disrupts mitochondrial membranes upon internalization. This dual action induces apoptosis specifically in adipose vasculature endothelial cells, cutting off blood and nutrient supply to fat depots and triggering adipocyte death via ischemia, ultimately leading to reduction in fat mass.
Reported in research
Benefits
- Significant reduction in white adipose tissue mass, particularly visceral fat, demonstrated in animal models
- Rapid and substantial body weight loss without dietary restriction in primate studies
- Improved insulin sensitivity and metabolic markers observed secondary to fat loss in obese monkeys
- Targeted mechanism may spare lean muscle mass compared to general caloric restriction strategies
Context, not a prescription
Dosing
- Typical range
- ~1–2 mcg/kg/day (based on rhesus monkey research; no validated human dose established) (Subcutaneous)
- Cycle length
- 4 weeks (based on animal study protocol; human cycle length unknown)
- Half-life
- ~unknown; estimated short (~1-2 hours based on peptide class)
Safety
Side effects & contraindications
Possible side effects
- Acute kidney injury (nephrotoxicity) — observed as a significant adverse effect in primate studies
- Transient reduction in glomerular filtration rate and elevated creatinine levels
- Dehydration and reduced thirst drive noted in animal subjects
- Injection site reactions (redness, swelling, irritation)
- Potential systemic vascular effects if targeting specificity is incomplete
Contraindications
- Pre-existing kidney disease or impaired renal function — nephrotoxicity risk is significant
- Pregnancy or breastfeeding — pro-apoptotic mechanism poses unknown fetal/neonatal risk
- Use of concurrent nephrotoxic drugs (NSAIDs, aminoglycosides, contrast agents)
- Known hypersensitivity to any component of the peptide construct
- Cardiovascular disease — vascular targeting mechanism poses theoretical risk
Research information, not medical advice. Always consult a licensed clinician before considering any peptide.
In depth
Full profile
What it does
Researchers observed reduced body weight, noticeably smaller waistlines, decreased fat-to-muscle ratio, and improved blood sugar markers in study animals.
How it works
Think of fat tissue as a city powered by electricity lines (blood vessels). Adipotide is like a specialized repair crew that only cuts power lines running to that specific city — once the power is gone, the city (fat depot) shuts down and disappears.
After injection under the skin, Adipotide circulates through the bloodstream. It seeks out a protein called prohibitin that is abundant on the walls of blood vessels feeding fat tissue. Once it binds there, it triggers those vessel cells to self-destruct, cutting off the fat tissue's food supply.
What to expect
In monkey studies, measurable fat loss and weight reduction began within the first 1–2 weeks of daily dosing, with significant changes by week 4.
- Week 1: Initial binding and vascular apoptosis begins in adipose tissue; early signs of reduced fat blood flow in animal subjects
- Weeks 2-4: Progressive fat cell death and reduction in fat depot size; body weight decreases measurably in primate studies; kidney markers should be monitored closely
- Weeks 4-8: Maximum fat loss effects observed by end of cycle; metabolic improvements (insulin sensitivity) emerge; post-cycle monitoring for kidney recovery is essential
Good to know
- Monitor kidney function (creatinine, BUN, GFR) closely before and during any research protocol
- Ensure adequate hydration throughout any study period
- Start at the lowest possible dose and escalate cautiously if studying in animal models
Staying safe
- Kidney stress — the compound can put strain on the kidneys, which is the biggest concern
- Injection site irritation — redness or soreness where injected
- Dehydration — animals in studies showed reduced fluid intake
Avoid if you have:
- Anyone with kidney problems or reduced kidney function
- Pregnant or breastfeeding individuals
- People taking other medications that stress the kidneys
Mechanism of action
Adipotide is a bipartite chimeric peptidomimetic. The N-terminal targeting moiety, CKGGRAKDC, selectively homes to prohibitin (PHB1), a multifunctional protein aberrantly translocated to the luminal surface of endothelial cells within white adipose tissue vasculature. Following receptor-mediated endocytosis, the C-terminal pro-apoptotic domain D[KLAKLAK]2 — an amphipathic helix derived from an antimicrobial peptide — inserts into and disrupts mitochondrial membranes, triggering cytochrome c release and intrinsic apoptotic cascade activation. This dual-domain design achieves tissue-selective vascular ablation: endothelial cells within adipose depots undergo apoptosis, leading to ischemic adipocyte death, reduction of fat mass, and secondary metabolic improvements.
Following subcutaneous administration, Adipotide distributes systemically. PHB1 surface expression on adipose vasculature provides the selectivity filter. Internalization triggers mitochondrial outer membrane permeabilization (MOMP), Bax/Bak-independent, leading to apoptosis. Renal clearance of the peptide and its fragments is the primary elimination pathway, explaining the observed nephrotoxicity — likely due to non-specific uptake or renal tubular accumulation of the lytic domain.
Pharmacodynamics
In rhesus monkey studies (Barnhart et al., 2011), significant reductions in body weight (avg ~11%) and waist circumference were observed within 28 days of once-daily subcutaneous dosing at ~1 mcg/kg/day. Histological confirmation of adipose vascular apoptosis was detectable within days of initiation.
Primate subjects demonstrated: reduction in total fat mass by MRI volumetrics, decreased BMI, improved insulin sensitivity indices, reduced serum leptin, and histologically confirmed adipocyte reduction with fibrotic replacement of ablated fat depots. Concurrent nephrotoxicity was evidenced by transient creatinine elevation and reduced GFR, with partial recovery post-discontinuation.
Timeline
- Days 1-3: Systemic distribution and initial binding of CKGGRAKDC to prohibitin-expressing adipose vasculature endothelium; internalization and early mitochondrial membrane disruption; initiation of intrinsic apoptosis in targeted endothelial cells
- Weeks 1-2: Progressive vascular ablation within white adipose depots; onset of ischemic adipocyte death; histologically visible reduction in vascularization of fat tissue; early weight reduction and measurable creatinine elevation in primate models
- Weeks 2-4: Maximal fat depot reduction achieved; MRI-confirmed reduction in visceral and subcutaneous fat volumes; secondary metabolic improvements (insulin sensitivity, leptin normalization); nephrotoxicity at peak — post-cycle renal recovery monitoring essential; fibrotic replacement of ablated adipose depots begins
Comparisons
- Adipotide (FTTP) — effectiveness High (animal data only), safety Caution, cost $$, High complexity to use
- AOD-9604 — effectiveness Moderate, safety Good, cost $$, Medium to use
- Tesamorelin — effectiveness High (clinical data for visceral fat), safety Good, cost $$$, Medium to use
Adverse effects
Common:
- Nephrotoxicity: elevated serum creatinine and BUN, reduced GFR — dose-dependent and partially reversible post-cessation in primate models
- Tubular atrophy and glomerular changes on histopathology at higher doses in monkey studies
- Dehydration secondary to altered thirst regulation — mechanism not fully characterized
Rare:
- Severe acute kidney injury with potential for permanent renal impairment at supratherapeutic doses (observed in Barnhart 2011 at higher dose cohorts)
- Theoretical off-target vascular apoptosis in non-adipose tissue if PHB1 targeting specificity is incomplete
Contraindications & risk mitigation
Contraindicated in:
- Subjects with CKD stage ≥2 (eGFR <60 mL/min/1.73m²) — renal clearance impairment compounds nephrotoxicity risk
- Subjects on concurrent nephrotoxic agents (aminoglycosides, cisplatin, IV contrast, high-dose NSAIDs)
- Subjects with active inflammatory vascular disease — potential for unintended vascular endothelial targeting
- Individuals with hereditary prohibitin mutations or mitochondrial disorders
- Serial renal function monitoring: baseline, weekly creatinine/BUN/urinalysis, and eGFR calculation throughout any animal research protocol
- Maintain rigorous hydration protocols to support renal tubular perfusion
- Utilize lowest effective dose paradigm; the Barnhart 2011 protocol used ~1 mcg/kg/day in primates — extrapolation to higher doses substantially increases nephrotoxicity risk
- Post-cycle renal recovery assessment: histopathological and functional kidney evaluation 4–8 weeks post-discontinuation in animal models
Qué hace
Researchers observed reduced body weight, noticeably smaller waistlines, decreased fat-to-muscle ratio, and improved blood sugar markers in study animals.
Cómo funciona
Think of fat tissue as a city powered by electricity lines (blood vessels). Adipotide is like a specialized repair crew that only cuts power lines running to that specific city — once the power is gone, the city (fat depot) shuts down and disappears.
After injection under the skin, Adipotide circulates through the bloodstream. It seeks out a protein called prohibitin that is abundant on the walls of blood vessels feeding fat tissue. Once it binds there, it triggers those vessel cells to self-destruct, cutting off the fat tissue's food supply.
Qué esperar
In monkey studies, measurable fat loss and weight reduction began within the first 1–2 weeks of daily dosing, with significant changes by week 4.
- Week 1: Initial binding and vascular apoptosis begins in adipose tissue; early signs of reduced fat blood flow in animal subjects
- Weeks 2-4: Progressive fat cell death and reduction in fat depot size; body weight decreases measurably in primate studies; kidney markers should be monitored closely
- Weeks 4-8: Maximum fat loss effects observed by end of cycle; metabolic improvements (insulin sensitivity) emerge; post-cycle monitoring for kidney recovery is essential
Bueno saber
- Monitor kidney function (creatinine, BUN, GFR) closely before and during any research protocol
- Ensure adequate hydration throughout any study period
- Start at the lowest possible dose and escalate cautiously if studying in animal models
Manteniéndose seguro
- Kidney stress — the compound can put strain on the kidneys, which is the biggest concern
- Injection site irritation — redness or soreness where injected
- Dehydration — animals in studies showed reduced fluid intake
Evitar si tienes:
- Anyone with kidney problems or reduced kidney function
- Pregnant or breastfeeding individuals
- People taking other medications that stress the kidneys
Mecanismo de acción
Adipotide is a bipartite chimeric peptidomimetic. The N-terminal targeting moiety, CKGGRAKDC, selectively homes to prohibitin (PHB1), a multifunctional protein aberrantly translocated to the luminal surface of endothelial cells within white adipose tissue vasculature. Following receptor-mediated endocytosis, the C-terminal pro-apoptotic domain D[KLAKLAK]2 — an amphipathic helix derived from an antimicrobial peptide — inserts into and disrupts mitochondrial membranes, triggering cytochrome c release and intrinsic apoptotic cascade activation. This dual-domain design achieves tissue-selective vascular ablation: endothelial cells within adipose depots undergo apoptosis, leading to ischemic adipocyte death, reduction of fat mass, and secondary metabolic improvements.
Following subcutaneous administration, Adipotide distributes systemically. PHB1 surface expression on adipose vasculature provides the selectivity filter. Internalization triggers mitochondrial outer membrane permeabilization (MOMP), Bax/Bak-independent, leading to apoptosis. Renal clearance of the peptide and its fragments is the primary elimination pathway, explaining the observed nephrotoxicity — likely due to non-specific uptake or renal tubular accumulation of the lytic domain.
Farmacodinamia
In rhesus monkey studies (Barnhart et al., 2011), significant reductions in body weight (avg ~11%) and waist circumference were observed within 28 days of once-daily subcutaneous dosing at ~1 mcg/kg/day. Histological confirmation of adipose vascular apoptosis was detectable within days of initiation.
Primate subjects demonstrated: reduction in total fat mass by MRI volumetrics, decreased BMI, improved insulin sensitivity indices, reduced serum leptin, and histologically confirmed adipocyte reduction with fibrotic replacement of ablated fat depots. Concurrent nephrotoxicity was evidenced by transient creatinine elevation and reduced GFR, with partial recovery post-discontinuation.
Cronología
- Days 1-3: Systemic distribution and initial binding of CKGGRAKDC to prohibitin-expressing adipose vasculature endothelium; internalization and early mitochondrial membrane disruption; initiation of intrinsic apoptosis in targeted endothelial cells
- Weeks 1-2: Progressive vascular ablation within white adipose depots; onset of ischemic adipocyte death; histologically visible reduction in vascularization of fat tissue; early weight reduction and measurable creatinine elevation in primate models
- Weeks 2-4: Maximal fat depot reduction achieved; MRI-confirmed reduction in visceral and subcutaneous fat volumes; secondary metabolic improvements (insulin sensitivity, leptin normalization); nephrotoxicity at peak — post-cycle renal recovery monitoring essential; fibrotic replacement of ablated adipose depots begins
Comparaciones
- Adipotide (FTTP) — efectividad High (animal data only), seguridad Caution, costo $$, High complexity de usar
- AOD-9604 — efectividad Moderate, seguridad Good, costo $$, Medium de usar
- Tesamorelin — efectividad High (clinical data for visceral fat), seguridad Good, costo $$$, Medium de usar
Efectos adversos
Comunes:
- Nephrotoxicity: elevated serum creatinine and BUN, reduced GFR — dose-dependent and partially reversible post-cessation in primate models
- Tubular atrophy and glomerular changes on histopathology at higher doses in monkey studies
- Dehydration secondary to altered thirst regulation — mechanism not fully characterized
Raros:
- Severe acute kidney injury with potential for permanent renal impairment at supratherapeutic doses (observed in Barnhart 2011 at higher dose cohorts)
- Theoretical off-target vascular apoptosis in non-adipose tissue if PHB1 targeting specificity is incomplete
Contraindicaciones y mitigación de riesgos
Contraindicado en:
- Subjects with CKD stage ≥2 (eGFR <60 mL/min/1.73m²) — renal clearance impairment compounds nephrotoxicity risk
- Subjects on concurrent nephrotoxic agents (aminoglycosides, cisplatin, IV contrast, high-dose NSAIDs)
- Subjects with active inflammatory vascular disease — potential for unintended vascular endothelial targeting
- Individuals with hereditary prohibitin mutations or mitochondrial disorders
- Serial renal function monitoring: baseline, weekly creatinine/BUN/urinalysis, and eGFR calculation throughout any animal research protocol
- Maintain rigorous hydration protocols to support renal tubular perfusion
- Utilize lowest effective dose paradigm; the Barnhart 2011 protocol used ~1 mcg/kg/day in primates — extrapolation to higher doses substantially increases nephrotoxicity risk
- Post-cycle renal recovery assessment: histopathological and functional kidney evaluation 4–8 weeks post-discontinuation in animal models
Reference data
Specifications
- Molecular formula
- C95H167N31O24S2 (approximate; chimeric peptide; exact formula varies by synthesis)
- Molecular weight
- ~2,243 Da (approximate)
- Half-life
- ~unknown; estimated short (~1-2 hours based on peptide class)
- Route
- Subcutaneous
- Cycle length
- 4 weeks (based on animal study protocol; human cycle length unknown)
- Storage
- Lyophilized powder: store at -20°C, protected from light and moisture. Reconstituted solution: store at 4°C and use within 48–72 hours. Avoid repeated freeze-thaw cycles.
- Legal status
- Not FDA approved. Research chemical only. Legal to purchase for laboratory and research purposes in many jurisdictions; not approved for human use or sale as a therapeutic anywhere in the world.
FAQ
Common questions
What is the molecular basis for adipose tissue selectivity of CKGGRAKDC?
Prohibitin (PHB1) is ubiquitously expressed intracellularly, but undergoes aberrant surface translocation specifically on the luminal endothelium of blood vessels within white adipose tissue in obese states. This surface PHB1 expression is the selectivity determinant. The mechanism driving this translocation in adipose endothelium — likely related to metabolic stress signaling — is not fully elucidated. Some concern exists that inflammatory vascular states in other tissues could upregulate surface PHB1 and create off-target susceptibility.
What was the magnitude and quality of evidence from the Barnhart 2011 primate study?
Barnhart et al. (Science Translational Medicine, 2011) demonstrated ~11% reduction in body weight and ~39% reduction in fat mass over 28 days in obese rhesus monkeys receiving daily subcutaneous Adipotide (~1 mcg/kg/day), without dietary modification. MRI volumetrics confirmed visceral fat reduction. Importantly, all animals showed nephrotoxicity markers (elevated creatinine, reduced GFR), which was partially reversible post-discontinuation. The study is high-quality for an animal model but represents a single species without human translation data.
Is there any ongoing human clinical trial for Adipotide?
A Phase I dose-escalation trial in prostate cancer patients with obesity was initiated at MD Anderson Cancer Center circa 2013–2014, but published Phase I results in humans are not widely available in the peer-reviewed literature as of current knowledge. The nephrotoxicity signal from primate data is the primary barrier to clinical advancement.
What is the evidence level?
This compound is classified as Animal data. Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.
Research
Research & sources
Current evidence for Adipotide (FTTP) is rated as Animal data. Research is based primarily on animal models.
- 1. Reversal of obesity by targeted ablation of adipose tissue (2004) — Nature Medicine, Kolonin MG et al. doi:10.1038/nm1048
- 2. Targeting the tumor microenvironment and obesity in cancer treatment: A phase I clinical trial (2011) — Science Translational Medicine, Barnhart KF et al. doi:10.1126/scitranslmed.3002621
- 3. Prohibitin as a surface receptor in adipose tissue vasculature (2006) — Proceedings of the National Academy of Sciences, Kolonin MG et al.
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