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Synthetic nootropics & research compounds

Dihexa

Dihexa (PNB-0408; angiotensin IV analog)

Dihexa is an experimental angiotensin IV-derived research compound, also called PNB-0408, studied mainly in cell and animal models for synaptogenesis and memory-related outcomes. It is not a conventional dietary supplement, approved medicine, or validated nootropic. No reliable human dose, onset, duration, long-term safety profile, or clinical cognitive benefit was found. The proposed HGF/c-Met pathway is also a cancer-biology pathway, so c-Met activation should be handled as a serious mechanism-based caution rather than a marketing point.

Neurotrophic PathwaysIsolated CompoundSyntheticSemi SyntheticMostly Animal EvidenceMostly In Vitro EvidenceEmerging Research
Updated August 2026/5 min read/8 citations
Reviewed by the NootropicsIndex editorial team.Method: prioritize cited human research and official safety or regulatory sources; compare retailer-listed prices without endorsing products.Affiliate disclosure
01

What is it?

Experimental angiotensin IV analog

2

Dihexa is an angiotensin IV-derived experimental compound designed to be orally active and blood-brain-barrier penetrant in preclinical work. It is sold online as a research chemical, but that market presence does not establish human suitability, legal status, purity, or nootropic efficacy.

No human nootropic validation7
No reliable human Dihexa trial, dose, pharmacokinetic profile, onset window, effect duration, or long-term safety dataset was found. The positive evidence should be described as animal/cell research only.
02

Names, aliases and forms

Common NameDihexa
Research CodesPNB-0408; AngIV analog
Chemical NameN-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide
Molecular FormulaC27H44N4O5
Pubchem Cid129010512
InchikeyXEUVNVNAVKZSPT-JTJYXVOQSA-N
03

Mechanisms of action

HGF/c-Met activation is the core mechanism claim

2

The key preclinical paper reports that Dihexa binds HGF and that Dihexa-related procognitive/synaptogenic effects depend on HGF/c-Met pathway activation. This is a mechanistic research finding, not a human benefit claim.

c-Met is also a cancer-biology pathway

6

HGF/c-Met signaling is widely studied in oncogenesis and cancer therapy. That does not prove Dihexa causes cancer, but it makes casual human use especially hard to justify without safety data.

04

Potential effects and evidence map

Dihexa evidence is preclinical. PubMed-indexed studies report HGF/c-Met-dependent synaptogenic and procognitive effects in experimental systems and APP/PS1 mouse work, and a systematic review of angiotensin IV analogs summarizes non-human cognition models. These findings do not establish human nootropic efficacy, dosing, pharmacokinetics, or safety. ClinicalTrials.gov searches for Dihexa and PNB-0408 found no human studies suitable for supplement-style claims.

Effect domainMagnitudeGrade
Memory / learning3
UnknownConfidence: Low

Dihexa has animal memory and synaptogenesis signals, but no reliable human memory or learning evidence.

Note Keep all positive claims preclinical and model-specific.

1/5
D
Cellular / long-term brain support2
UnknownConfidence: Low

HGF/c-Met and synaptogenesis findings are mechanistic and preclinical, not validated human brain-support outcomes.

Note The pathway also creates safety uncertainty.

1/5
D
Focus / attention7
UnknownConfidence: High

No reliable human evidence supports Dihexa as a focus or attention enhancer.

Note No acute focus/onset claim should be made.

0/5
E
Mood / wellbeing7
UnknownConfidence: High

No reliable human mood or wellbeing evidence was found for Dihexa.

Note Avoid extrapolating from animal cognition models.

0/5
E
05

Typical dosages and timing

Research compound7Not established

Do not convert rodent doses, forum reports, or vendor serving suggestions into a human nootropic dose. Dihexa lacks reliable public human dosing, frequency, route, cycling, and safety boundaries.

06

Timing & effect horizon

Effect horizonUnknown
Unknown
Onset, duration and half-life are not established7

No reliable human onset, duration, half-life, or washout value was found. Any vendor or user timing claim should be considered unsupported unless tied to verifiable human data.

07

Safety, side effects and risk profile

Research-chemical risk dominates6
The main safety issue is not a known common side effect profile; it is the absence of human safety data combined with a growth-factor mechanism, unknown purity, unknown dose-response, and uncertain legal status.
Legal / regulatory risk7
Confidence: High

Dihexa is a research compound, not a conventional dietary supplement or approved public-use nootropic; listings may be legally risky or not for human use.

Note Do not infer legality, importability, or human-use permission from vendor availability.

4/5
D
Evidence uncertainty4
Confidence: High

No human dose, safety profile, efficacy, onset, duration, or long-term outcome data were found for Dihexa.

Note Evidence uncertainty is central to the page.

4/5
D
Interaction risk6
Confidence: Medium

Avoid unsupervised use with cancer history, growth-factor pathway concerns, neurologic disease, pregnancy, or complex medication regimens.

Note This is a mechanism-based caution around HGF/c-Met biology and unknown human pharmacology, not a proven human adverse-event profile.

3/5
D
Pregnancy / lactation caution7
Confidence: High

Avoid during pregnancy or lactation; no human safety basis exists for Dihexa in these contexts.

Note Research compounds without human safety data should be avoid-first in pregnancy and lactation.

4/5
E
No safety margin6Unknown

People with cancer history, active tumors, neurologic disease, immune or growth-factor pathway concerns, pregnancy, lactation, or complex medication regimens should not use Dihexa without specialist oversight. There is no supplement-style safety margin to rely on.

08

Legal and regulatory status

United States - FDA compounding context, as of August 20268

FDA lists dihexa acetate among bulk drug substances that may present significant safety risks in U.S. compounding. FDA says it has not identified human exposure data on drug products containing dihexa acetate and lacks important information about possible harm in humans. This is a U.S.- and dihexa-acetate-specific context, not an international legality ruling or an approval determination for every Dihexa product.

09

Practical buying and quality notes

  • For Dihexa, a low price per milligram is not useful if identity, purity, solvent residues, stability, storage, and legal status are unclear. If a listing lacks recent third-party analytical testing, consider it unknown material.1
  • Product rows and price links can help document market availability, but they should not be read as a recommendation to buy or use Dihexa. The evidence and safety sections should be reviewed before comparing any offer.7
10

FAQ

Is Dihexa a proven nootropic?

7

No. Dihexa has animal and cell evidence related to memory models and synaptogenesis, but no reliable human nootropic validation was found.

What Dihexa dose is established for humans?

7

None. No reliable human dose, frequency, cycle length, onset, duration, or route was found. Rodent doses and vendor suggestions should not be converted into human instructions.

Why is c-Met mentioned as a caution?

6

Dihexa research centers on HGF/c-Met pathway activation, and c-Met is also important in cancer biology. This is a mechanism-based uncertainty warning, not proof of a specific human adverse outcome.

Are Dihexa listings proof that it is legal?

7

No. Online availability does not establish legality, importability, product identity, or permission for human use. Check the exact jurisdiction and product documentation before drawing any conclusion.

11

References

  1. PubChem. Dihexa, CID 129010512. Accessed 2026-06-30.
  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. Journal of Pharmacology and Experimental Therapeutics. 2014;351(2):390-402.
  3. Sun X, Deng Y, Fu X, Wang S, Duan R, 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(11):1487.
  4. Ho JK, Nation DA. Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. Neuroscience and Biobehavioral Reviews. 2018;92:209-225.
  5. Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW. Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. Journal of Pharmacology and Experimental Therapeutics. 2011;339(1):35-44.
  6. Maulik G, Shrikhande A, Kijima T, Ma PC, Morrison PT, Salgia R. Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine & Growth Factor Reviews. 2002;13(1):41-59.
  7. ClinicalTrials.gov search results for Dihexa and PNB-0408. Accessed 2026-06-30.
  8. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. Accessed 2026-08-21.

Legacy catalog references are also retained in the website database.

Note

This page is informational and summarizes available evidence. It is not medical advice, a recommendation, or a substitute for guidance from a qualified clinician.