What is a dual COA and why is it critical for Dihexa research?

A dual COA means two independent, lot-specific Certificates of Analysis: (1) HPLC purity confirming ≥99% chemical identity, and (2) LAL endotoxin assay confirming LPS levels. Dihexa research relies on cell-viability, spinogenesis, and c-Met phosphorylation assays — all critically confounded by trace LPS contamination activating TLR4. Neither ProSpec nor SwissChems provides a LAL endotoxin COA per lot.

How does PureRawz's lot verification portal work?

Every PureRawz vial carries a unique lot number. Enter it at officialpurerawz.us/verify to retrieve both COA documents, the testing lab name, and QC release date for your exact batch — useful for IRB submissions and publication methodology sections.

What is the difference between Dihexa and its parent compound angiotensin IV?

Angiotensin IV (AngIV) is an endogenous hexapeptide with poor blood-brain barrier penetration and rapid enzymatic degradation in plasma (half-life minutes). Dihexa was synthesised by modifying the AngIV analog Nle1-AngIV to add hexanoic acid (N-hexanoyl) at the N-terminus and replace the C-terminus with a 6-aminohexanoic amide — dramatically increasing lipophilicity, BBB penetrability, and metabolic stability (plasma half-life ~335 minutes in preclinical models).

Dihexa

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Buy Dihexa | ≥99% Pure | Dual COA | PureRawz USA

⚠ RESEARCH USE ONLY: All PureRawz products are strictly for in-vitro laboratory research. Not for human or animal consumption. Not FDA-approved. For use by qualified researchers only.
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≥99% Purity — HPLC Verified

Dual COA — HPLC + LAL Endotoxin

Unique Lot Numbers — Full Traceability

USA Manufactured & Third-Party Tested

Ships USA in 1 Business Day

✓ HPLC COA

✓ LAL COA

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Lot: DX-2025-0089
QC: 2025-12-01
≥99.4% HPLC

Research Peptide · Angiotensin IV Analog · HGF/c-Met Modulator

Buy Dihexa —
≥99% Purity + Dual COA

When you buy Dihexa from PureRawz, every vial ships with two independent Certificates of Analysis — HPLC purity verification and an LAL endotoxin assay — traceable to a unique batch lot number. ProSpec certifies only 97% purity with zero endotoxin data. SwissChems provides no per-lot LAL testing. PureRawz is the USA-based dual-COA standard. Ships in 1 business day. No prescription required.

≥99% HPLC Purity
LAL Endotoxin Tested
Unique Lot Number
USA Manufactured
Ships in 1 Business Day

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per vial · free shipping $[THRESHOLD]+

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View Both COAs

In-stock orders ship same business day — USA domestic only

Technical Data

Full Product Specifications

All data verifiable via lot-specific COA documents included with every order.

Compound Name	Dihexa (PNB-0408)
IUPAC / Full Name	N-hexanoic-Tyr-Ile-(6) aminohexanoic amide
Synonyms	PNB-0408, N-(1-oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-L-isoleucinamide
Amino Acid Sequence	Hexanoyl-Tyr-Ile-Ahx-NH₂
Molecular Formula	C₂₇H₄₄N₄O₅
Molecular Weight	504.7 g/mol
CAS Number	1401708-83-5
PubChem CID	129010512
Purity (HPLC)	≥99% — third-party verified per lot
Endotoxin (LAL)	Tested — COA included per lot
Physical Appearance	White lyophilised (freeze-dried) powder
Solubility	DMSO, sterile water, PBS (≥100 µg/mL)
Storage	−20 °C, desiccated, protected from light
Stability Note	Lipophilic structure — avoid RT exposure; degrade within 12–18 h at room temp
Shelf Life	36 months under proper storage
Lot Traceability	Unique lot number — every vial, every batch
Manufacturing	USA (domestic synthesis and lyophilisation)
Testing	Independent third-party laboratory
Shipping	1 business day · USA domestic only
Intended Use	In-vitro laboratory research only

Quality Assurance

Why PureRawz Provides a Dual COA — And Why It Matters for Dihexa Research

ProSpec certifies only 97% purity by RP-HPLC with no endotoxin data — and ships at room temperature. SwissChems provides no per-lot purity statement or LAL data on its Dihexa page. PureRawz issues two separate, lot-specific COAs on every batch — because Dihexa's c-Met phosphorylation, spinogenesis, and cell-viability assays are the exact assay types most severely corrupted by trace endotoxin contamination.

HPLC Purity Certificate

High-Performance Liquid Chromatography separates and quantifies every molecular species in the sample. PureRawz Dihexa consistently measures ≥99% purity per lot — versus ProSpec's 97% RP-HPLC standard. For c-Met binding assays performed at picomolar concentrations, a 2% impurity difference can produce measurable false-signal artefacts. The full chromatogram PDF is available for download with every order.

≥99% purity confirmed per lot

LAL Endotoxin Assay Certificate

The Limulus Amebocyte Lysate (LAL) assay detects bacterial LPS that HPLC cannot identify. Dihexa is studied at picomolar concentrations in spinogenesis and c-Met phosphorylation assays — the same concentration range at which sub-nanogram LPS activates TLR4 on microglia and macrophages, producing false neuroinflammatory signals. A clean LAL COA is the only safeguard. Neither ProSpec nor SwissChems provides this documentation per lot.

LAL endotoxin tested — per lot

Both COA documents are lot-number-specific. Download from the product page or retrieve via officialpurerawz.us/verify.

Research Background

What Is Dihexa?

Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide; CAS 1401708-83-5) is a synthetic oligopeptide derived from angiotensin IV (AngIV) — a hexapeptide fragment of the renin-angiotensin system known to influence cognitive function via central nervous system receptors. It was developed at Washington State University by Dr. Joseph W. Harding's laboratory through systematic structural modification of the AngIV analog Nle¹-AngIV, with the explicit goal of creating an orally active, blood-brain barrier-penetrant compound with metabolic stability far exceeding that of its endogenous parent.

The key structural modifications — addition of a hexanoyl (N-hexanoic acid) group at the N-terminus and replacement of the C-terminal carboxyl with a 6-aminohexanoic amide — dramatically increase lipophilicity and reduce enzymatic vulnerability. In preclinical pharmacokinetic models, these changes extend plasma half-life to approximately 335 minutes, compared to minutes for AngIV itself. Dihexa's lipophilicity also enables it to achieve brain-to-plasma concentration ratios exceeding 1.0 following oral administration in rodent models.

Dihexa's primary research interest lies in its mechanism: it functions as an allosteric potentiator of hepatocyte growth factor (HGF), binding HGF with a dissociation constant of approximately 65 picomolar and amplifying HGF's ability to activate the c-Met receptor tyrosine kinase. This makes it a unique tool for studying synaptogenesis, dendritic spine density, and structural plasticity in isolation from neurotransmitter modulation pathways.

Important research note: The 2014 Benoist et al. paper (J Pharmacol Exp Ther) establishing the HGF/c-Met mechanism was retracted in April 2025 due to image integrity concerns. However, an independent 2021 study (Chai et al., Brain Sciences) confirmed cognitive improvements in APP/PS1 Alzheimer's transgenic mice via the PI3K/Akt signalling pathway and remains in good standing. Researchers should cite current literature accordingly.

Mechanistic Science

Mechanism of Action — Six Research Pathways

All findings are from in-vitro or animal studies only. Researchers should note the 2025 retraction of Benoist et al. (2014) and should rely on post-2021 independent literature for citation purposes.

HGF Allosteric Potentiation & c-Met Phosphorylation

Dihexa binds hepatocyte growth factor (HGF) with high affinity (Kd ~65 pM) at the hinge region, facilitating HGF dimerisation — a prerequisite for c-Met receptor binding and activation. In the presence of subthreshold HGF concentrations, Dihexa restores full c-Met phosphorylation, augmenting HGF-dependent cell scattering and intracellular kinase cascades in HEK-293T cell models.

Harding lab, WSU; Chai et al., Brain Sciences 2021 [1]

Hippocampal Spinogenesis & Synaptogenesis

In dissociated hippocampal neuron cultures, Dihexa at picomolar concentrations induces dendritic spinogenesis and synaptogenesis equivalent to suprathreshold HGF. Post-mortem hippocampal analyses in rodent models report dendritic spine density increases of 40–60% in CA1 and dentate gyrus, with electron microscopy confirming functional synapse formation including presynaptic vesicle clustering and postsynaptic density maturation.

Independent preclinical literature; Chai et al. 2021 [1]

PI3K/Akt Signalling Cascade

c-Met activation by Dihexa triggers the PI3K/Akt intracellular pathway — a major pro-survival, anti-apoptotic signalling axis. In the APP/PS1 Alzheimer's transgenic mouse model (Chai et al., 2021), Dihexa restored spatial learning and cognitive function via this pathway, with improved Morris water maze performance correlating with hippocampal Akt phosphorylation levels.

Chai et al., Brain Sciences 2021 [1]

MAPK/ERK Pathway & Structural Protein Synthesis

The MAPK/ERK cascade, activated downstream of c-Met, translocates to the nucleus and upregulates transcription factors (CREB, Elk-1) driving expression of structural synaptic proteins — PSD-95 (postsynaptic density scaffolding), synaptophysin (presynaptic vesicle marker), spinophilin, and GAP-43 (axonal sprouting). Histological analyses confirm elevated expression of these markers in hippocampal CA1 and dentate gyrus following Dihexa administration.

Preclinical histological analyses, multiple models

Long-Term Potentiation (LTP) Enhancement

Dihexa augments hippocampal long-term potentiation — the synaptic strengthening mechanism underlying memory consolidation — in aged rodent models (18–24 months), restoring LTP amplitudes to levels observed in young adult animals. Cognitive benefits in preclinical models persist 2–4 weeks after treatment cessation, consistent with stable structural synaptic changes rather than transient neurotransmitter modulation.

Rodent LTP studies, Harding lab literature

Neuroprotection & Anti-inflammatory Activity in TBI Models

In controlled cortical impact TBI models in rats, Dihexa administration beginning 24 hours post-injury reduced lesion volume by 25–30% and improved motor coordination recovery (rotarod). Immunohistochemistry revealed increased doublecortin (neurogenesis marker) in the SVZ and dentate gyrus, alongside reduced Iba1-positive activated microglia in perilesional cortex — suggesting both neurogenic and anti-inflammatory research dimensions.

TBI preclinical model literature

Unique to PureRawz

Batch Traceability — Our Public Lot Verification Portal

ProSpec ships Dihexa at room temperature with 97% purity and no endotoxin data. SwissChems provides no per-lot COA for Dihexa on their product page. PureRawz provides full per-lot documentation — publicly verifiable — because Dihexa's extreme picomolar potency makes batch integrity non-negotiable for reproducible research.

Every vial is traceable to a specific, independently tested batch.

Enter the lot number printed on your vial at officialpurerawz.us/verify and retrieve:

The HPLC purity COA PDF for your exact batch
The LAL endotoxin COA PDF for your exact batch
The name of the independent third-party testing laboratory
The QC release date and synthesis batch ID
Documentation suitable for IRB submissions and publication methodology sections

Sample Lot Number

DX-2025-0089

Compound: Dihexa
Batch: #89 · QC Released
Purity: ≥99.4% HPLC

Verify at /verify →

Supplier Comparison

PureRawz vs. Competitors — Dihexa Side-by-Side

Based on publicly available supplier information as of April 2026.

Feature	PureRawz ✦	ProSpec Bio	SwissChems
Purity Standard	≥99% HPLC	Only 97% RP-HPLC	Not stated per lot
HPLC Purity COA	✔ Per lot — downloadable PDF	RP-HPLC listed on page	✗ No Dihexa-specific COA shown
LAL Endotoxin COA	✔ Per lot — full assay	✗ Not provided	✗ Not provided
Unique Lot Number Per Vial	✔ Every vial	✗ Not mentioned	✗ Not mentioned
Public Lot Verification Portal	✔ officialpurerawz.us/verify	✗	✗
USA Based / USA Shipping	✔ Domestic USA only	✗ Israel-based	✗ Iceland-based (.is domain)
Ships in 1 Business Day (USA)	✔	✗ International transit	✗ International transit
Cold-Chain Shipping	✔	✗ Ships at room temp	Not stated
Trust Badge Strip on Page	✔ 5 badges	✗ None	2 basic badges
FAQ Section (Schema Rich Results)	✔ 10 Q&As	✗	✗
Research Background on Page	✔ Full MOA + refs	Brief background only	✗ Generic compound description
No Prescription Required	✔	✔	✔
HPLC Refund Guarantee	✔	✗ Not stated	✔

✦ PureRawz. Data from publicly available pages, April 2026. Subject to change.

Related Research Compounds

Researchers Studying Dihexa Also Explore

Frequently Asked Questions

Dihexa Research FAQ

For research and educational purposes only. Nothing here constitutes medical advice.

What is Dihexa and what is it used for in research?+

Dihexa (CAS 1401708-83-5) is a synthetic oligopeptide derived from angiotensin IV, developed at Washington State University. In laboratory settings it is studied for HGF/c-Met receptor activation, hippocampal spinogenesis and synaptogenesis, PI3K/Akt and MAPK/ERK pathway modulation, dendritic arborization, long-term potentiation (LTP) enhancement, and neuroprotection in traumatic brain injury and Alzheimer's disease models. All research use is strictly in-vitro or preclinical.

What purity does PureRawz Dihexa have and how does it compare to competitors?+

PureRawz Dihexa is manufactured to ≥99% purity as measured by HPLC per lot by an independent third-party laboratory. ProSpec Bio certifies only 97% purity by RP-HPLC — a meaningful difference for c-Met receptor binding assays performed at picomolar concentrations where even 1–2% impurity can generate measurable off-target signals. SwissChems does not state a per-lot purity figure on their Dihexa product page. PureRawz is the only supplier of the three providing both HPLC and LAL endotoxin COAs per lot.

What is a dual COA and why is it especially critical for Dihexa research?+

A dual COA means two independent, lot-specific Certificates of Analysis: (1) HPLC purity confirming ≥99% chemical identity, and (2) LAL endotoxin assay confirming bacterial LPS levels. This is especially critical for Dihexa research because the compound is studied at picomolar concentrations in spinogenesis and c-Met phosphorylation assays — precisely the concentration range at which trace LPS contamination (sub-nanogram) activates TLR4 on microglia and macrophages, producing false neuroinflammatory signals that can mimic or mask Dihexa's actual effects on synaptic markers. Neither ProSpec nor SwissChems provides LAL data per lot.

What happened to the Benoist et al. 2014 Dihexa paper?+

The 2014 Benoist et al. paper published in the Journal of Pharmacology and Experimental Therapeutics, which established the HGF/c-Met mechanism for Dihexa, was formally retracted in April 2025 due to image integrity concerns involving co-author Leen Kawas. However, an independent 2021 study by Chai et al. (Brain Sciences, PMID: 34827487) confirmed cognitive improvements in APP/PS1 Alzheimer's transgenic mice via the PI3K/Akt signalling pathway and remains in good standing. The original 2013 McCoy synthesis paper received an expression of concern but has not been retracted. Researchers should cite post-2021 independent literature for current work.

How quickly does PureRawz ship Dihexa and where do you ship?+

All in-stock PureRawz orders ship within 1 US business day from our domestic USA facility. This is especially significant for Dihexa: its lipophilic structure makes it more vulnerable to degradation than standard peptides, beginning to degrade within 12–18 hours at room temperature. ProSpec is Israel-based and ships at room temperature — both factors that risk compound integrity in transit. SwissChems is Iceland-based. PureRawz ships domestically within the USA only with temperature-appropriate handling. No prescription required.

How should I store Dihexa in my laboratory?+

Store lyophilised Dihexa at −20 °C or below in a sealed desiccated container away from light. Dihexa's lipophilic modifications make it more vulnerable to oxidative degradation than standard peptides — ProSpec notes only 3-week room-temperature stability, significantly less than proper frozen storage. Once reconstituted, aliquot into single-use quantities and freeze at −20 °C immediately. Avoid repeated freeze-thaw cycles. Shelf life under proper conditions is 36 months lyophilised.

What solvents are recommended for reconstituting Dihexa?+

Dihexa dissolves in DMSO or aqueous solutions (sterile water, PBS) aided by its lipophilic residues. Recommended starting concentration ≥100 µg/mL. For cell-based assays, dilute DMSO stocks to keep final DMSO below 0.1% v/v to avoid cytotoxicity artefacts. Adding 0.1% BSA or HSA as a carrier protein is recommended for solutions stored beyond 24–48 hours to prevent adsorption to tube walls.

What does "10 million times more potent than BDNF" mean for Dihexa?+

This figure originates from laboratory molar potency comparisons measuring spinogenesis induction — how many molecules of each compound are needed to produce comparable synapse formation in hippocampal cell cultures. BDNF and Dihexa act through different receptors (TrkB vs HGF/c-Met) and downstream pathways, making the comparison context-specific rather than a general claim of superiority. Researchers should treat this as a finding about molar efficiency in specific assay conditions, not a definitive statement about cognitive enhancement in complex biological systems.

Is Dihexa a controlled substance in the United States?+

As of April 2026, Dihexa is not scheduled under the US Controlled Substances Act and is not FDA-approved for any medical use. PureRawz sells Dihexa exclusively as an in-vitro research reagent for qualified researchers. Regulations are subject to change — always verify current regulatory status with your institution's compliance office before purchasing or handling.

Does PureRawz offer bulk or institutional purchasing for Dihexa?+

Yes. Academic institutions, CROs, and qualified research organisations may contact PureRawz for bulk pricing, custom lot sizes, and institutional invoicing. All bulk orders include the same dual COA quality assurance (HPLC purity + LAL endotoxin) and unique lot traceability as standard orders. Contact our research team via the support page for a custom quote.

Scientific Literature

References

Chai S-Y et al. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sciences. 2021;11(12):1555. PMID: 34827487 — Independent confirmation; currently in good standing.
McCoy AT et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141–154. PMID: 23076063 — Expression of concern issued; not retracted.
Benoist CC et al. Cognition-enhancing and neuroprotective activity of a novel angiotensin IV analog. J Pharmacol Exp Ther. 2014. PMID: 25187433 — Retracted April 2025. Cited here for historical context only.
Wright JW, Harding JW. The brain hepatocyte growth factor/c-Met receptor system: a new target for the treatment of Alzheimer's disease. J Alzheimers Dis. 2015;45(4):985–1000. PMID: 25633668
Harding JW et al. Facilitation of the Brain HGF/c-Met Receptor System: A New Approach to Treat Alzheimer's Disease? Austin J Clin Neurol. 2016;3(1):1086.

⚠ Research Use Only — Full Disclaimer: All PureRawz products, including Dihexa, are furnished for in-vitro laboratory research purposes only. These products are not medicines, pharmaceuticals, or dietary supplements. They have not been approved by the US Food and Drug Administration (FDA) to diagnose, treat, cure, or prevent any medical condition, disease, or ailment. Bodily introduction of any kind into humans or animals is strictly prohibited by law. All purchases are limited to licensed researchers and qualified professionals. Any information provided on this page is for scientific and educational purposes only and does not constitute medical, clinical, veterinary, or professional advice. Full Terms & Conditions →

Dihexa

Dihexa is a powerful nootropic research compound commonly explored for cognitive enhancement, memory studies, neurogenesis support, and advanced laboratory applications.
Browse related Purerawz products and trusted scientific references below.

Research References

PubMed Research Database
– scientific studies and published research
National Center for Biotechnology Information (NCBI)
– biomedical and research resources
U.S. Food and Drug Administration
– regulatory and compliance reference

Additional information

Attributes	Powder 500mg, Powder 1000mg, Liquid 30ml/17mg per ml/500mg, Tablets 20mg per tablet/27ct/540mg, Tablets 20mg per tablet/54ct/1080mg

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Dihexa

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≥99% Purity + Dual COA

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