Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)
Cognitive · HGF/c-Met activator (mechanism unverified post-retraction)
Tier D
High-risk evidence profile
Bottom line
Read Off Label grades Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) as D (3.1/10) based on preclinical evidence, unclear benefit magnitude, and a med-high-risk safety profile.
Its high-risk evidence profile reflects a Safety score of 3.5/10; reported benefits and harms can differ by indication, dose, route, duration, and population.
Originally developed at WSU (Harding lab); commercialized via Athira Pharma as fosgonimeton/ATH-1017 — a subcutaneous prodrug rapidly converted to dihexa.
Studied, labeled, or reported-use context: No established human dosing for dihexa itself; fosgonimeton was 40 mg SC daily in LIFT-AD — Research chem; not individualized guidance.
Frontier potential — editorial judgment, not evidence
This is a separate axis from the grade above. It asks a different question: if this worked in humans, how much would it matter? It is our judgment, it is not part of the composite score, and it cannot raise a grade. A high number here is a statement about the idea, not about whether it works or whether anyone should take it.
What the ceiling rests on
An angiotensin IV analogue reported to be orders of magnitude more potent than BDNF at promoting synaptogenesis in preclinical models, with striking results in animal models of cognitive impairment. If a fraction of that potency translated it would be a significant compound.
Why it may not get there
There is no human data of any kind. A potent synaptogenic agent is exactly the class where uncontrolled growth is a serious theoretical concern, and the HGF/c-Met pathway it acts through is implicated in oncogenesis. It is sold as a research chemical with no safety file whatsoever, which is a materially different situation from an unproven drug in development.
What would change this Any formal preclinical toxicology package, let alone a human trial.
If you were testing this on yourself
Two properties decide whether an n-of-1 experiment is readable and recoverable. These describe the experiment — they are not a judgment about whether to run it, and nothing here is a recommendation.
Can you undo it?
Potentially permanent
A potent synaptogenic agent acting through a pathway implicated in oncogenesis, with no toxicology package of any kind in humans. Unknown, and structurally the sort of unknown that would not be reversible.
Can you tell if it worked?
Nothing you can measure
No endpoint exists that you could observe for the reason this is taken. An experiment without a readout cannot tell you anything, however it turns out.
What would fool you No human data, no safety file, and a research-chemical supply chain with unverified identity. There is nothing here to measure and no basis for judging what you would be taking.
What the evidence says
Originally developed at WSU (Harding lab); commercialized via Athira Pharma as fosgonimeton/ATH-1017 — a subcutaneous prodrug rapidly converted to dihexa. Four 2024-2026 events reshape this entry. (1) Sept 2024: Athira's LIFT-AD Phase 2/3 in mild-to-moderate AD missed primary (Global Statistical Test p=0.70) and key secondary endpoints; ACT-AD Phase 2 had already failed; Athira discontinued the program. (2) April 2025: JPET retracted both foundational mechanism papers (Kawas 2012; Benoist 2014) after WSU investigation confirmed "falsified and/or fabricated data"; Kawas and Harding named as solely responsible. (3) Jan 2025: Athira paid $4.07M DOJ settlement (False Claims Act — failure to disclose research misconduct in NIH grant applications). (4) April 22 2026: FDA removed dihexa acetate from 503A Category 2 ("Do Not Compound") pending PCAC review by Feb 2027; this is NOT an approval and is being misrepresented by compounders/sellers as legitimization. Net for the biohacker audience: a heavily hyped nootropic ("10 million times stronger than BDNF") whose mechanism rests on retracted papers; whose pharmaceutical version failed Phase 2/3 in humans; and which has no long-term human safety data. The theoretical c-Met cancer concern is now more weighty because c-Met activation is a validated oncogenic driver targeted by multiple FDA-approved cancer drugs (capmatinib; tepotinib; crizotinib). The ~12.7-day serum half-life means adverse events cannot be rapidly reversed by stopping. The evidence base is weakened by retracted mechanism papers, a failed related clinical program, and absent long-term human safety data.
Mechanism
Angiotensin IV analog originally proposed as an HGF dimerization mimetic / c-Met activator promoting synaptogenesis and dendritic spine formation; foundational mechanism papers (Kawas 2012; Benoist 2014) were RETRACTED by JPET in April 2025 for falsified/fabricated data — the HGF/c-Met mechanism is now formally unverified; reported serum half-life ~12.7 days (slow washout)
Studied, labeled, or reported dose & route
No established human dosing for dihexa itself; fosgonimeton was 40 mg SC daily in LIFT-AD
This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.
Citations
- neurologylive.com
- jpet.aspetjournals.org
- jpet.aspetjournals.org
- retractionwatch.com
- fda.gov
- PubMed · PMID 22297356
- patents.google.com
A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.
Common questions
- What does the evidence show about Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)'s effects?
- Read Off Label rates the evidence for Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) as Preclinical and the benefit magnitude as unclear, producing an overall grade of D (3.1/10). Originally developed at WSU (Harding lab); commercialized via Athira Pharma as fosgonimeton/ATH-1017 — a subcutaneous prodrug rapidly converted to dihexa.
- What safety findings are reported for Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)?
- Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) has a med-high risk profile in the database. Med-High (theoretical oncogenic risk from c-Met activation; ~12.7-day half-life means no rapid discontinuation if adverse events emerge; no long-term human safety data for dihexa itself) Legal status: Research chem (not FDA-approved; April 22 2026 removed from FDA 503A Category 2 "Do Not Compound" list pending PCAC review before Feb 2027 — removal is NOT approval).
- What does the low Safety score for Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) represent?
- The Safety score is 3.5/10. It records the substantial harms described for one or more use contexts; the Benefit score, indication, dose, route, duration, population, and legal status remain separate parts of the evidence profile.
- What doses or routes are reported for Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)?
- No established human dosing for dihexa itself; fosgonimeton was 40 mg SC daily in LIFT-AD This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
- How does Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) work?
- Angiotensin IV analog originally proposed as an HGF dimerization mimetic / c-Met activator promoting synaptogenesis and dendritic spine formation; foundational mechanism papers (Kawas 2012; Benoist 2014) were RETRACTED by JPET in April 2025 for falsified/fabricated data — the HGF/c-Met mechanism is now formally unverified; reported serum half-life ~12.7 days (slow washout)
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.