Side-by-side · Research reference

AdipotidevsDihexa

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED15/49 cited

BAnimal-StrongHUMAN-REVIEWED7/28 cited

Adipotide

Pro-apoptotic Vascular-Targeting Peptide · Preclinical Only

PreclinicalStatus

PHB1TargetHossen 2013

ApoptosisMechanismHossen 2013

IV · Systemic · Preclinical Protocols OnlyHossen 2013

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

01Mechanism of Action

Parameter

Adipotide

Dihexa

Primary target

Prohibitin-1 (PHB1) on adipose vasculature endotheliumHossen 2013

c-Met receptor (HGF receptor tyrosine kinase)

Pathway

CKGGRAKDC domain binds PHB1 → Peptide internalisation → D(KLAKLAK)₂ mitochondrial membrane disruption

HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization

Downstream effect

Endothelial apoptosis → Adipose vascular collapse → Adipocyte involution → Weight loss

Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models

Feedback intact?

N/A — Direct apoptotic mechanism, non-hormonal

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Origin

Synthetic bioconjugate: PHB1-targeting homing peptide + pro-apoptotic KLA sequence

Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015

Antibody development

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02Dosage Protocols

Parameter

Adipotide

Dihexa

Animal dose (mouse)

Low dose (not specified in abstract)Hossen 2013

Systemic injection in diet-induced obesity (DIO) models.Hossen 2013

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Route

Intravenous (systemic injection)

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Frequency

Not specified in available data

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Evidence basis

Preclinical animal models only

Pre-clinical / Rodent models

Human data

None — no clinical trials reported

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Human dosing

—

Not established — no human trials

Animal studies

—

Mouse/rat models only — dosing not translatable to humans

Clinical status

—

No Phase 1, 2, or 3 trials published

03Metabolic / Fat Loss Evidence

Parameter

Adipotide

Dihexa

Primary fat target

White adipose tissue (all depots)

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Mechanism

Vascular apoptosis → adipose blood supply collapse → adipocyte deathHossen 2013

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Body weight reduction

Significant reduction in DIO miceHossen 2013

Absolute values not provided in abstract.

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Leptin levels

Significant decrease

Parallel to adipose mass reduction.

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Effect on adipocytes

Antiobesity effect on dysfunctional adipose cells (adipocytes + macrophages)Hossen 2013

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Ectopic fat

Reduction in ectopic fat depositionHossen 2013

Marker of dysfunctional adipose tissue / metabolic syndrome.

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Species tested

Obese rhesus monkeys, DIO mice

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Human translation

Unknown — no clinical trials

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04Side Effects & Safety

Parameter

Adipotide

Dihexa

Safety profile

Unknown — preclinical data only

—

Vascular selectivity

Targets adipose vasculature; off-target vascular effects unknown

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Apoptotic mechanism risk

Pro-apoptotic payload may affect unintended tissues if selectivity incomplete

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Kidney / liver toxicity

Not reported in available data

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Immunogenicity

Not assessed in available data

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Human safety data

—

None available — no human clinical trials

Theoretical c-Met risks

—

c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile

Pre-clinical tolerability

—

Not systematically reported in available studies

Absolute Contraindications

Adipotide

·Human use — not approved, no clinical safety data

Dihexa

·Not approved for human use — research compound only

Relative Contraindications

Adipotide

·Any condition requiring intact adipose-tissue vascularisation

Dihexa

·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)

05Administration Protocol

Parameter

Adipotide

Dihexa

1. Route

Intravenous injection (systemic) in preclinical models. No human protocols exist.

No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.

2. Formulation

Bioconjugate peptide. May also be encapsulated in nanoparticles (prohibitin-targeted nanoparticle formulation, KLA-PTNP, showed superior efficacy vs. free bioconjugate in mice).Hossen 2013

Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.

3. Preclinical dosing

Low-dose systemic injection (exact dosing not specified in available abstract). Frequency and duration not detailed.Hossen 2013

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4. Storage

Not specified — likely requires peptide-grade lyophilised storage and reconstitution.

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