Dihexa
Also known as: PNB-0408
Molecular Identifiers
Molecular Formula
C27H44N4O5
CAS Number
1401708-83-5
PubChem CID
129010512Molecular Weight
504.67 Da
Overview
Potent cognitive enhancer, angiotensin IV analog. Activates the HGF/c-Met pathway, promoting synaptogenesis and neurotrophism. Considered up to 10 million times more potent than BDNF in forming new synaptic connections in preclinical studies.
The interest in Dihexa lies in its pro-cognitive potential: as a modified analog of angiotensin IV, it activates the HGF/c-Met pathway, promoting synaptogenesis, new neural connection formation, and improved synaptic plasticity. It has been described in preclinical models as capable of exceeding by several orders of magnitude the activity of classical neurotrophins such as BDNF in promoting new synapses, with studies in models of Alzheimer's and cognitive deficits.
It has no approval as a medicine by the FDA, EMA, or ANVISA, and remains an experimental compound in preclinical investigation. In the market it appears as a product labeled for research, with little effective regulation, used in off-label nootropic contexts. There are also reports of oral bioavailability, atypical for a peptidomimetic, which has broadened its appeal.
It was developed in the laboratory of Joseph Harding at Washington State University, within a research line on angiotensin IV analogs for neuroprotection. Human clinical trials are not yet consolidated, and translation of the preclinical effects to clinical use remains open.
Within the peptide nootropic group, Dihexa stands out for its mechanism (HGF/c-Met agonism, synaptogenesis) and its reported oral bioavailability, atypical compared with Selank/Semax (intranasal/SC, GABAergic and BDNF modulation), Cerebrolysin (porcine hydrolysate IV/IM), and P21 (BDNF + anti-tau). Against PE 22-28 (TREK-1, depression), it acts on an independent neurotrophic target. Its human clinical evidence is, however, less consolidated than Selank, Semax, or Cerebrolysin.
N-Hexanoyl-Tyr-Ile-(6)-aminohexanoic amide Peptidomimetic — modified angiotensin IV derivative with hexanoyl and aminohexanoic chains
Half-life
~12 hours
Administration Route
Subcutaneous or oral
Category
Cognitive & Neuroprotective
Mechanism of Action
- Activation of the HGF/c-Met pathway (hepatocyte growth factor)
- Promotion of synaptogenesis and new neural connection formation
- Potent neurotrophic effect
- Prevention of HGF degradation by the heparanase enzyme
- Improvement of synaptic plasticity and spatial memory
Reported Side Effects
Adverse effects described in the literature. Severity and frequency vary between individuals.
- Headache
- Anxiety
- Insomnia
- Increased blood pressure (rare)
Product Properties
| Purity | >98% |
| Appearance | White lyophilized powder |
| Solubility | Soluble in water and bacteriostatic water |
| Source | Solid-phase peptide synthesis (SPPS) |
| Storage | Lyophilized: -20°C for up to 2 years, 2-8°C for up to 6 months. Reconstituted: 2-8°C for up to 4 weeks. Protect from light and moisture. Avoid repeated freeze-thaw cycles. |
Presentations & Preparation
Vials of Dihexa found in the research market:
Reconstitution
- Diluent: Bacteriostatic water
- Volume: 2 ml per vial
- Inject the diluent slowly against the vial wall
- Gently swirl until fully dissolved
- Never shake
- Also available in oral formulation for research
Storage
- Lyophilized: Refrigerated 2-8°C
- Reconstituted: Refrigerated 2-8°C (up to 30 days)
- Protect from direct light
- Do not freeze after reconstitution
Scientific Studies
Published studies on Dihexa.
AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y
The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System
Benoist CC, Kawas LH, Zhu M, Bhatt KA, Bhatt SJ, Bhatt JP, Wright JW, Harding JW
Related Peptides
Adamax
100-500 mcg via intranasal or subcutaneous · 1-2 times daily
Cerebrolysin
5-30 ml per injection · Once daily
Cortagen
DSIP
100-300 mcg per subcutaneous injection · Once daily
Epithalon
1-5 mg per subcutaneous injection (some protocols use 5-10 mg per full cycle) · Once daily or every other day
FG Loop
25-200 mg intranasal (single ascending dose Phase 1) · Single dose (tolerability study)