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Dihexa

L-Isoleucinamide,N-(1-oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-;N-(1-Oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-L-isoleucinamide;Dihexa;N-Hexanoic-Tyr-Ile-(6)aminohexanoic amide

1401708-83-5

C27H44N4O5

InChIKey=XEUVNVNAVKZSPT-JTJYXVOQSA-N

504.7

504.66

CNS Agents

1.111±0.06 g/cm3(Predicted)

866.2±65.0 °C(Predicted)

Angiotensin IV-derived oligopeptide / HGF-c-Met potentiator

Research compound — Not FDA approved

A synthetic, orally active, blood-brain-barrier-permeable oligopeptide (Hexanoyl-Tyr-Ile-Ahx-NH₂) derived from angiotensin IV. Dihexa binds hepatocyte growth factor (HGF) with high affinity (Kd = 65 pM) and allosterically potentiates HGF activity at its receptor c-Met, promoting dendritic spinogenesis and synaptogenesis. In preclinical models it was reported to be seven orders of magnitude more potent than BDNF at promoting synapse formation. Note: the foundational 2014 paper (McCoy AT, et al. Neurobiol Learn Mem. 2014) was retracted in 2025.

65 pM

Dihexa is an HGF potentiator, not a direct receptor agonist. It does not activate c-Met alone but markedly augments HGF-induced c-Met activation at low nanomolar HGF concentrations. Functional synaptogenic activity was reported at 10⁻¹°–10⁻⁻ M (original data now subject to retraction).

Original report: McCoy AT, et al. Neurobiol Learn Mem. 2014;115:112-120 (retracted 2025). Benoist CC, et al. J Pharmacol Exp Ther. 2014;351(3):628-637.

NCT04488419

PubChem

9WYX65A5C2

Benoist CC, et al. J Pharmacol Exp Ther. 2014 — HGF/c-Met mechanism; McCoy AT, et al. Neurobiol Learn Mem. 2014 — Synaptogenesis data (Retracted 2025); Athira Pharma: Fosgonimeton (prodrug) pipeline status

Dihexa is NOT FDA-approved or EMA-approved as a medicine. It is a research compound only. The foundational 2014 paper describing its synaptogenic potency was retracted in 2025. Its phosphate prodrug fosgonimeton failed a Phase 2/3 Alzheimer’s trial (LIFT-AD, 2024). This listing is for industrial and laboratory research use only. It is not medical advice, a clinical recommendation, or an approved therapy description. Always verify regulatory status, purity, and intended use with the supplier and applicable authorities before purchase or use.