Side-by-side · Research reference
DihexavsP21
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED7/28 cited
BAnimal-MechanisticHUMAN-REVIEWED8/36 cited
Dihexa
Angiotensin IV Analogue · Pre-Clinical
Not established — animal studies only
P21
CNTF-Derived Neuropeptide · Animal Model Evidence
Animal onlyEvidence level
SQ · Site unspecified · Frequency unknown
01Mechanism of Action
Parameter
Dihexa
P21
Primary target
c-Met receptor (HGF receptor tyrosine kinase)
CNTF receptor alpha (CNTFRα) / LIF receptor (LIFR) / gp130 complex on neural stem cells
Pathway
HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization
CNTF mimetic → CNTFRα/LIFR/gp130 heterotrimer → JAK/STAT3 signaling → neurogenesis, stem cell proliferation, neuroprotection
Downstream effect
Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models
Increased neural stem cell self-renewal, globose basal cell activation (Mash1+ cells), olfactory sensory neuron regeneration, hippocampal neurogenesis, neuroprotection in developmental disorders
Feedback intact?
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Origin
Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015
Small-molecule peptide mimetic derived from full-length ciliary neurotrophic factor (CNTF), designed to retain receptor activation with improved pharmacokineticsMottolese 2024
Antibody development
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02Dosage Protocols
Parameter
Dihexa
P21
Human dosing
Not established — no human trials
No established protocol
No clinical trial data available.
Animal studies
Mouse/rat models only — dosing not translatable to humans
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Evidence basis
Pre-clinical / Rodent models
Animal models only
CDKL5 KO mice, methimazole-induced olfactory injury, CNTF-/- knockout models.Mottolese 2024Cox 2026Jia 2020
Clinical status
No Phase 1, 2, or 3 trials published
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Animal models (mice)
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Dose and route not specified in abstractsMottolese 2024Jia 2020
In vitro and in vivo studies demonstrate efficacy; precise dosing protocols not disclosed.
Duration
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Not specified
Route
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Presumed subcutaneous or intraperitoneal (animal studies)
04Side Effects & Safety
Parameter
Dihexa
P21
Human safety data
None available — no human clinical trials
None available
No clinical trials in humans.
Theoretical c-Met risks
c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile
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Pre-clinical tolerability
Not systematically reported in available studies
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Animal tolerability
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Well-tolerated in mouse models; no toxicity reported in available abstracts
Theoretical risks
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Uncontrolled stem cell proliferation, immune response to peptide, unknown long-term CNS effects
Absolute Contraindications
Dihexa
- ·Not approved for human use — research compound only
P21
- ·Use in humans not validated
Relative Contraindications
Dihexa
- ·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)
P21
- ·Active malignancy (theoretical — neurotrophic signaling may affect tumour growth)
- ·Pregnancy or lactation (no safety data)
05Administration Protocol
Parameter
Dihexa
P21
1. Human administration
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.
Not established. No FDA approval, no clinical trial data.
2. Legal status
Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.
In vivo studies used systemic administration (route not specified in abstracts) in mouse models of neurodegeneration, olfactory injury, and CDKL5 deficiency disorder. In vitro studies used primary cell cultures.