Description
Dihexa (N-hexanoic-Tyr-Ile-(6) amino hexanoic amide) is a synthetic oligopeptide derived from angiotensin IV, a fragment of the renin-angiotensin system. It belongs to a class of angiotensin-based small molecules developed to probe the hepatocyte growth factor (HGF) / c-Met receptor signaling axis in the central nervous system [2]. Its relatively low molecular weight and reported blood-brain barrier permeability make it a distinctive tool compound within this peptide class [2][5].
At the mechanistic level, Dihexa binds HGF with high affinity and potentiates signaling through the c-Met receptor, a pathway linked to neurogenesis, dendritic arborization, and synaptogenesis in preclinical models [5]. Comparative neurotrophic assays have indicated that the compound operates at potencies several orders of magnitude beyond that of brain-derived neurotrophic factor (BDNF), underscoring the sensitivity of the HGF/c-Met axis to this ligand class [5]. Researchers also note its activity intersecting with broader neuroactive peptide signaling networks that modulate neuroplasticity-relevant pathways [1].
Laboratory investigations have focused primarily on its utility in animal models of cognitive impairment, where angiotensin IV analogs including Dihexa have been associated with improvements in spatial working memory and related behavioral endpoints [3]. Beyond neuroscience, Dihexa has attracted interest in stem cell biology, where it has been incorporated into small-molecule cocktail protocols designed to drive hepatic specification from human pluripotent stem cells in vitro [4]. This breadth of research applications reflects the compound's versatility as a molecular probe across multiple biological contexts.
References
[1] Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews, 2026. https://pubmed.ncbi.nlm.nih.gov/41490200/
[2] The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease. Journal of Alzheimer's disease : JAD, 2015. https://pubmed.ncbi.nlm.nih.gov/25649658/
[3] Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies. Neuroscience and biobehavioral reviews, 2018. https://pubmed.ncbi.nlm.nih.gov/29733881/
[4] Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy. Stem cell research & therapy, 2022. https://pubmed.ncbi.nlm.nih.gov/35410439/
[5] Dihexa. Wikipedia. https://en.wikipedia.org/wiki/Dihexa
