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database / nootropic

Dihexa

also known as N-hexanoic-Tyr-Ile-(6) aminohexanoic amide

preclinical nootropic nervous sequence not characterised
OOOOONNNNHHHHHH
36 heavy atoms · 80 bonds · drag to pan, scroll to zoom C27O5N4

Skeletal structure drawn from the computed atomic coordinates in PubChem CID 129010512. Carbons are implicit vertices; hydrogens on carbon are suppressed, as in any structural formula. Nothing here is estimated — every atom sits where PubChem placed it.

Research reference only. The observations below are recorded in the cited literature. Nothing here is advice or a recommendation, and no dosing information is published on this site.

Sequence

Primary structure not characterised in the public records this index draws on. Nothing is shown rather than something invented.

An angiotensin IV analogue built on non-standard hexanoic and aminohexanoic units — not a standard peptide sequence.

Molecular data

Chemical fields come from the PubChem compound record; computed values are derived from the sequence shown above.
molecular formulaC27H44N4O5
molecular weight504.7 Da (PubChem)
computed backbone massnot characterised
lengthnot characterised
net charge (pH 7.4)not characterised
mean hydropathynot characterised
half-lifenot characterised
delivery routenot characterised
PubChem CID129010512
PDBnot characterised
UniProt parentnot characterised

Mechanism

Angiotensin IV analogue studied as an HGF/c-Met potentiator in neural models.

Reported targets: HGF/c-Met

Experimental structure

No experimental structure of this peptide is deposited in the PDB. Nothing is rendered here — a predicted fold would not be a structure, and this site does not draw one.

Reported effects

Each row is an outcome described in the literature indexed for this peptide. Reported in the cited work — not a claim, not a recommendation.

Reported observations and the corpus they are drawn from.
reported outcomewhere it appears
synaptogenesis in modelsTherapeutic Peptides in Orthopaedics: Applications, Challenges, and Future D… Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews 2026
cognition in modelsSmall-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Plurip… Current protocols in stem cell biology 2016

Literature (8)

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions — Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews 2026

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived n…

open access ↗ · PMID 41490200 · DOI 10.5435/jaaosglobal-d-25-00236

Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells — Current protocols in stem cell biology 2016

abstract not reproduced — this record is not open-access, so it is linked rather than copied.

publisher record ↗ · PMID 27532814 · DOI 10.1002/cpsc.13

AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway — Brain sciences 2021

The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer's disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokine…

open access ↗ · PMID 34827486 · DOI 10.3390/brainsci11111487

Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents — The Journal of pharmacology and experimental therapeutics 2013

abstract not reproduced — this record is not open-access, so it is linked rather than copied.

publisher record ↗ · PMID 23055539 · DOI 10.1124/jpet.112.199497

Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies — Annals of medicine and surgery (2012) 2021

BackgroundOptimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model.Materials and methodsThere were 10 experimental groups (n = 6-8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200-400 μg/kg b.wt.), Dihexa ([dose redacted] b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1-2 week intervals post nerve repair until the study endpoint (16 weeks).ResultsThe sensory f…

open access ↗ · PMID 34703584 · DOI 10.1016/j.amsu.2021.102917

Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats — Journal of Huntington's disease 2024

abstract not reproduced — this record is not open-access, so it is linked rather than copied.

publisher record ↗ · PMID 38489193 · DOI 10.3233/jhd-231507

Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure — Frontiers in cellular neuroscience 2015

Loss of sensory hair cells from exposure to certain licit drugs (e.g., aminoglycoside antibiotics, platinum-based chemotherapy agents) can result in permanent hearing loss. Here we ask if allosteric activation of the hepatocyte growth factor (HGF) cascade via Dihexa, a small molecule drug candidate, can protect hair cells from aminoglycoside toxicity. Unlike native HGF, Dihexa is chemically stable and blood-brain barrier permeable. As a synthetic HGF mimetic, it forms a functional ligand by dimerizing with endogenous HGF to activate the HGF receptor and downstream signaling cascades. To evaluate Dihexa as a potential hair cell protectant, we used the larval zebrafish lateral line, which possesses hair cells that are homologous to mammalian inner ear hair cells and show similar responses to toxins. A dose-response relationship for Dihexa protection was established using two ototoxins, neo…

open access ↗ · PMID 25674052 · DOI 10.3389/fncel.2015.00003

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy — Stem cell research & therapy 2022

BackgroundVarious methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable.MethodsWe dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.ResultsWe demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute gro…

open access ↗ · PMID 35410439 · DOI 10.1186/s13287-022-02831-1

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