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Dihexa

PNB-0408 · N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

Nootropic & CNSPreclinical
From$5.00/mgCompare prices
MW
504.7g/mol
Formula
C27H44N4O5

Dihexa is a synthetic peptide derived from angiotensin IV, specifically designed to penetrate the blood-brain barrier and exhibit procognitive properties. Researchers primarily study dihexa for its potential role in enhancing cognitive function and synaptic connectivity, particularly in the context of neurodegenerative diseases such as Alzheimer's disease. Key findings from recent studies indicate that dihexa binds with high affinity to hepatocyte growth factor (HGF) and activates the c-Met receptor, leading to increased synaptogenesis and hippocampal spinogenesis. Additionally, preclinical evidence suggests that dihexa may facilitate memory consolidation and retrieval in animal models. Current research is focused on further elucidating its mechanisms of action and exploring its therapeutic potential in clinical settings.

Chemical Profile

Chemical Profile

Chemical structure
Chemical Structure
FormulaC27H44N4O5
Molecular Weight504.7 g/mol
CAS Number1401708-83-5
PubChem CID129010512

Half-Life

POOral

Poor bioavailability

Pharmacokinetic data is limited, with ongoing research to determine specific half-life values.

Mechanism

Mechanism of Action

Dihexa acts primarily through the hepatocyte growth factor (HGF) and c-Met receptor system, leading to the phosphorylation of c-Met and subsequent activation of signaling pathways involved in neuroplasticity, such as those promoting synaptogenesis and dendritic arborization. This mechanism enhances cognitive function and memory consolidation by facilitating the formation of new synaptic connections and augmenting hippocampal spinogenesis. While the precise details of its action remain to be fully elucidated, its effects are linked to critical biological processes such as neurogenesis and tissue repair.

Research

10 Research Publications

253

Total Citations

2

Human/RCT

2.6

Avg. Influence

2024

Latest

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#01

Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents.

AnimalInfluence4.0
50
The study demonstrated that dihexa, a metabolically stabilized angiotensin IV analog, exhibits significant procognitive effects in animal models, suggesting its potential as an antidementia agent.
PubMed
#02

The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases.

ReviewInfluence3.0
49
The review summarized that dihexa, a small molecule derived from angiotensin IV, shows promise in enhancing synaptic connectivity and addressing cognitive and motor dysfunctions in neurodegenerative diseases.
PubMed
#03

Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

Mathapati Santosh, et al. · Current protocols in stem cell biology · 2016

In VitroInfluence3.0
40
Researchers observed a new method to create liver-like cells from human stem cells using small molecules instead of traditional growth factors. This approach allows for more efficient and reproducible production of these cells, which are important for studying liver diseases and testing new drugs.

Key findings

  1. 01The study developed a protocol that uses small molecules to guide stem cells into liver-like cells.
  2. 02This method replaces the need for conventional growth factors, making the process more efficient.
  3. 03The resulting liver-like cells can be used for various applications in research and medicine.
PubMed
#04

The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.

Wright John W & Harding Joseph W · Journal of Alzheimer's disease : JAD · 2015

Review
36
The review highlighted that activation of the hepatocyte growth factor/c-Met receptor system by dihexa may facilitate synaptic connectivity and memory consolidation, presenting a potential therapeutic target for Alzheimer's disease.

Key findings

  1. 01Researchers observed that the c-Met receptor system plays a crucial role in neuron health and development.
  2. 02The compound Dihexa was shown to enhance the formation of new synaptic connections in animal models of Alzheimer's.
  3. 03Dihexa is orally active and can penetrate the blood-brain barrier, indicating its potential for memory improvement.
PubMed
#05

The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.

Benoist Caroline C, et al. · The Journal of pharmacology and experimental therapeutics · 2014

AnimalInfluence1.0
36
The study demonstrated that dihexa enhances procognitive activity through high-affinity binding to hepatocyte growth factor and subsequent c-Met phosphorylation, promoting synaptogenesis in the presence of subthreshold HGF concentrations.

Key findings

  1. 01Dihexa binds strongly to a growth factor called hepatocyte growth factor (HGF) and activates its receptor, c-Met.
  2. 02Both dihexa and another related compound promote the growth of new synapses in the brain, similar to HGF.
  3. 03The cognitive benefits of dihexa were blocked when HGF activity was inhibited, indicating its role in enhancing learning and memory.
PubMed
#06

Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure.

Uribe Phillip M, et al. · Frontiers in cellular neuroscience · 2015

Human
15
Researchers studied a compound called Dihexa to see if it could protect sensory hair cells from damage caused by certain antibiotics. They found that Dihexa effectively shields these cells from toxicity, suggesting it may have potential for preventing hearing loss related to chemical exposure.

Key findings

  1. 01Dihexa provides optimal protection to hair cells from aminoglycoside antibiotics at a concentration of 1 μM.
  2. 02The protective effect of Dihexa is linked to its activation of the hepatocyte growth factor (HGF) signaling pathway.
  3. 03Small chemical changes to Dihexa can significantly impact its protective abilities, highlighting the importance of its structure.
PubMed
#07

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

Pan Tingcai, et al. · Stem cell research & therapy · 2022

In VitroInfluence2.0
12
The study demonstrated that a small-molecule cocktail including dihexa can effectively induce hepatic specification from human pluripotent stem cells, producing functional hepatocyte-like cells for potential therapeutic applications.

Key findings

  1. 01The small-molecule cocktail CIP effectively induced the formation of definitive endoderm, a crucial step in liver cell development.
  2. 02Combining Vitamin C, Dihexa, and Forskolin successfully replaced growth factors to promote liver cell specification.
  3. 03The resulting liver cells displayed characteristics of mature liver cells and were capable of repopulating injured liver tissue in animal models.
PubMed
#08

Dimeric DOTA-alpha-melanocyte-stimulating hormone analogs: synthesis and in vivo characteristics of radiopeptides with high in vitro activity.

Bapst Jean-Philippe, et al. · Journal of receptor and signal transduction research · 2007

In Vitro
12
The study demonstrated that while dimeric alpha-MSH analogs showed high in vitro receptor affinity, their in vivo uptake by melanoma tumors was lower than expected, with increased kidney uptake.

Key findings

  1. 01Dimeric peptides showed higher binding affinity to melanoma cells in laboratory tests compared to a standard peptide.
  2. 02In living organisms, the dimeric peptides had lower tumor-to-kidney uptake ratios than the standard peptide.
  3. 03Increased kidney uptake of the dimeric peptides may limit their effectiveness for melanoma targeting.
PubMed
#09

Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies.

Weiss Jessica B, et al. · Annals of medicine and surgery (2012) · 2021

Animal
2
Researchers investigated the effects of stem cells, Granulocyte-Colony Stimulating Factor (G-CSF), and Dihexa on limb recovery after nerve damage in rats. They found that these treatments significantly improved sensory and motor function in the affected limbs over time, suggesting their potential as supportive therapies for nerve repair.

Key findings

  1. 01Sensory function in the rats returned to nearly normal levels by eight weeks after treatment.
  2. 02Motor function showed significant improvement when stem cells were combined with G-CSF or Dihexa.
  3. 03The recovery of nerve function varied, with some nerves regaining function more quickly than others.
PubMed
#10

Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.

Wells Russell G, et al. · Journal of Huntington's disease · 2024

Animal
1
The study demonstrated that dihexa did not mitigate 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats, indicating a lack of efficacy in this model.

Key findings

  1. 01PNB-0408 did not protect rats from weight loss induced by the toxin.
  2. 02The compound failed to improve motor function in rats exposed to the toxin.
  3. 03Cognitive abilities, including spatial learning and memory, were not preserved by PNB-0408 in this study.
PubMed
Safety

Safety & Handling

Research Gaps

No randomized controlled human trials have been conducted to evaluate the efficacy and safety of dihexa in humans. Additionally, the long-term effects of dihexa on cognitive function and potential side effects remain unclear, as well as the precise molecular mechanisms by which it enhances synaptogenesis and memory consolidation.

Solubility

Dihexa is soluble in DMSO and has limited solubility in water.

Storage & Handling

Lyophilized

Stable for 2+ years at -20°C, 12 months at 4°C

Reconstituted

Use within 14 days when refrigerated at 4°C

Avoid

Avoid repeated freeze-thaw cycles, direct light

Solvent

Bacteriostatic water or sterile saline recommended

Safety information is derived from published research and may not reflect all known risks. This is not medical advice.

Legal Status

Legal Status

🇩🇪DE

Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.

🇺🇸US

Not approved by the FDA. Not scheduled by the DEA.

🇦🇺AU

Not listed in the TGA schedules.

🇬🇧UK

Not approved by the MHRA as a medicinal product.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Community Insights

Community Insights

Publications per Year

9 total
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Pricing

Price Comparison

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Mechanism

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Mechanism

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Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer