Dihexa 10mg

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Dihexa 10 mg — research-grade lyophilized peptide powder in a sealed glass vial. This synthetic peptidomimetic, also designated PNB-0408, was engineered from the Angiotensin IV hexapeptide scaffold for enhanced metabolic stability, oral bioavailability, and blood-brain barrier penetration [1]. It is one of the most extensively studied small-molecule potentiators of the Hepatocyte Growth Factor (HGF)/c-Met signaling system in preclinical neuroscience.

Research Use Only: All products are intended exclusively for laboratory and scientific research. Not for human or veterinary use.

RESEARCH GRADE

Dihexa 10 mg Lyophilized Powder

Parameter

Value

Form

Lyophilized peptide powder

Content

10 mg Dihexa per vial

Packaging

Glass vial with sterile closure

Storage

Store lyophilized at 2–8 °C (desiccated, protect from light)

Molecular formula

$C_{27}H_{44}N_4O_5$

Molecular weight

~504.66 g·mol⁻¹

Sequence

N-hexanoyl-Tyr-Ile-Ahx-NH2

CAS number

1401708-83-5

In laboratory workflows, lyophilized research peptides are typically diluted with suitable solvents such as Acetic acid 0.6% – 10 ml. For diluting lyophilized peptide powders, you need a solution such as Acetic acid 0.6% – 10 ml .

What Is Dihexa?

Dihexa (N-hexanoyl-Tyr-Ile-(6)-aminohexanoic amide) is a rationally designed, metabolically stabilized analog of Angiotensin IV. Developed at Washington State University, it was built by truncating Angiotensin IV to its essential pharmacophore and adding lipophilic N- and C-terminal modifications to improve druglike properties [1].

How It Works — Mechanism of Action

Dihexa binds directly to Hepatocyte Growth Factor (HGF) with picomolar affinity (Kd = 65 pM) and potentiates HGF’s ability to activate its receptor, c-Met [2]. At subthreshold HGF concentrations where the growth factor alone is inactive, Dihexa markedly augments c-Met phosphorylation and downstream signaling [2]. c-Met activation in the central nervous system is associated with:

• Dendritic spine formation and synaptogenesis in hippocampal neurons [1,2]

• Neurogenesis and neuronal survival signaling [4]

• Anti-inflammatory actions (reduced IL-1β, TNF-α; increased IL-10) in neuroinflammation models [3]

• Neuroprotection against excitotoxic and traumatic insults [5,6]

Key Research Findings

Procognitive Activity: Oral Dihexa reversed scopolamine-induced spatial learning deficits in rats and improved memory performance in aged rats with natural cognitive decline. Effects were dose-dependent across oral, intraperitoneal, and intracerebroventricular routes [1].

Alzheimer’s Disease Models: In APP/PS1 transgenic mice (a widely used AD model), 3-month oral Dihexa treatment rescued spatial memory, reduced neuroinflammatory markers, inhibited glial activation, and increased synaptophysin expression via the PI3K/AKT pathway [3].

Neuroprotection: Dihexa protected sensory neurons from aminoglycoside-induced toxicity in zebrafish via HGF-dependent signaling [5] and improved working memory after repetitive mild traumatic brain injury in rats [6].

Nerve Repair: In a sciatic nerve injury model, Dihexa (2–4 mg/kg, 16 weeks) promoted limb functional recovery, suggesting potential in peripheral nerve regeneration research [7].

Important: All evidence for Dihexa is preclinical (in vitro and animal studies). No human clinical trials of Dihexa itself have been published. A related HGF/c-Met–modulating compound (fosgonimeton/ATH-1017) has entered human clinical trials for neurodegenerative diseases, providing indirect translational support for this mechanism [4].

Safety Considerations for Researchers

No human safety data exist for Dihexa. Researchers should be aware of the following theoretical considerations:

• The HGF/c-Met pathway is a recognized oncogenic signaling axis in multiple cancer types. The long-term effects of sustained c-Met potentiation are unknown [4,8].

• No chronic toxicity, reproductive toxicity, or carcinogenicity studies have been published for Dihexa.

• Dihexa has a long circulating half-life in rats [1]; human pharmacokinetics are uncharacterized.

• This compound is a research chemical, not an approved drug or dietary supplement.

References:

1. McCoy AT, Benoist CC, Wright JW, Kawas LH, Bule-Ghogare JM, Zhu M, Appleyard SM, Wayman GA, Harding JW. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013 Jan;344(1):141–154. PMID: 23055539. DOI: 10.1124/jpet.112.199497. [⚠️ Notice of Concern: JPET Sept 2021]

2. Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA, Harding JW. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther. 2014 Nov;351(2):390–402. PMID: 25187433. DOI: 10.1124/jpet.114.218735. [⚠️ Notice of Concern: JPET Sept 2021]

3. Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y. AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway. Brain Sci. 2021 Nov 11;11(11):1487. PMID: 34827486. DOI: 10.3390/brainsci11111487.

4. 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: 25649658. DOI: 10.3233/JAD-142814.

5. Uribe PM, Kawas LH, Harding JW, Coffin AB. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure. Front Cell Neurosci. 2015 Jan 28;9:3. PMID: 25674052. DOI: 10.3389/fncel.2015.00003.

6. Weiss JB, Phillips CJ, Malin EW, Gorantla VS, Harding JW, Salgar SK. Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model. Ann Med Surg (Lond). 2021 Oct 8;71:102917. PMID: 34703584. DOI: 10.1016/j.amsu.2021.102917.

7. Alzheimer’s Drug Discovery Foundation. Dihexa: Cognitive Vitality Report. Available at: https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Dihexa_1.pdf. Accessed February 2026.

8. Mulcahy EQX, Colomt RRC, Abounader R. HGF/MET Signaling in Malignant Brain Tumors. Int J Mol Sci. 2020;21(20):7546. PMID: 33066305. DOI: 10.3390/ijms21207546.

Evidence & Limitations Disclaimer

This product is sold exclusively for laboratory research and collector’s purposes. It is not a drug, dietary supplement, food, or cosmetic product. The scientific information provided on this page is derived from peer-reviewed preclinical studies and is intended for educational purposes only. All evidence for Dihexa is from in vitro and animal research; no human clinical trials have been published. The safety profile in humans is entirely unknown. Claims on this page are not intended to diagnose, treat, cure, or prevent any disease. Key foundational references [1,2] carry editorial Notices of Concern regarding possible image manipulation; independent replications [3,5,6] support the core findings through separate experimental approaches. Researchers are advised to consult the primary literature and institutional biosafety guidelines before use.

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Limitless BioChem is a trusted supplier of research compounds. Our products meet strict quality standards and are compliant with EU requirements. We focus on the safe and reliable supply of peptides and pure compounds intended exclusively for research or collector purposes.

This product is not intended for human or veterinary use. It is for collection or research purposes only. It cannot be used as food, dietary supplement or medicine! The information provided in the text on this page is for educational purposes only and does not constitute medical or other advice.