Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide)
Cognitive · HGF/c-Met activator (mechanism unverified post-retraction)
Tier D
What this is
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. Updated framing: skeptical-by-default.
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)
Dose & route
No established human dosing for dihexa itself; fosgonimeton was 40 mg SC daily in LIFT-AD
Citations
- https://www.neurologylive.com/view/synaptic-agent-fosgonimeton-falls-short-phase-2-3-lift-ad-trial-mild-moderate-alzheimers
- https://jpet.aspetjournals.org/article/S0022-3565(24)18845-3/fulltext
- https://jpet.aspetjournals.org/content/378/3/311
- https://retractionwatch.com/2021/09/24/four-papers-by-athira-ceo-earn-expressions-of-concern/
- https://www.fda.gov/media/94155/download
- https://pubmed.ncbi.nlm.nih.gov/22297356/
- https://patents.google.com/patent/US8598118B2/en
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