Dihexa

Quick answers

Molecular Profile

Type

Synthetic peptidomimetic (modified tripeptide-like angiotensin IV analog)

Molecular formula

C27H44N4O5

Molecular weight

~504.66 g/mol

CAS number

1401708-83-5

Fatty acid chain

N-terminal hexanoyl cap (hexanoic acid)

Sequence

N-hexanoic-Tyr-Ile-(6)aminohexanoic amide

Modification

N-terminal hexanoyl cap replacing the N-terminal residue of norleucine1-AngIV; C-terminal 6-aminohexanoic amide moiety replacing the His-Pro-Phe segment; designed to eliminate peptidase-sensitive bonds and increase metabolic stability and blood-brain-barrier permeance.

Mechanism & Target Class

Dihexa is a peptidomimetic in the angiotensin IV (AngIV) analog class, engineered from norleucine1-angiotensin IV by retaining the Tyr-Ile pharmacophore identified as the procognitive core and replacing peptidase-labile termini with an N-terminal hexanoyl cap and a C-terminal 6-aminohexanoic amide. These modifications confer increased hydrophobicity, metabolic stability, and blood-brain-barrier permeability. Mechanistic studies proposed that Dihexa acts at the level of the hepatocyte growth factor (HGF)/c-Met receptor tyrosine kinase system — specifically at HGF dimerization and availability — with downstream readouts examined in PI3K/Akt and MAPK/ERK signaling. Historically, the parent AngIV system was associated with the AT4 binding site, later identified as insulin-regulated aminopeptidase (IRAP); the shift toward an HGF/c-Met framing is a contested element of the literature, and the key papers asserting direct HGF binding were subsequently retracted.

Storage & Handling

Lyophilized

Store dry and sealed; short term at 0–4 °C, long term at −20 °C.

Handling

Dry compound reported stable at ambient shipping temperatures for short periods. Batch molecular weight may vary with degree of hydration. For research use only.

Primary Database

PubChem CID 129010512 ↗

References (21)

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8. Primary research

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   DOI: 10.1089/neur.2025.0053

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21. 21

    Albiston AL, McDowall SG, Matsacos D, et al. (2001). Journal of Biological Chemistry

    DOI: 10.1074/jbc.C100512200

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