Skip to content

Free UPS 2-Day shipping on orders over $150

Ri18 Labs
← Research articles

Neuroscience · Dihexa

Dihexa: an angiotensin IV analog acting on the HGF/c-Met system

October 4, 2026 · 1 min read · Models: Rat, Cell culture

Dihexa is a metabolically stabilized derivative of angiotensin IV developed at Washington State University. It has been studied in rat scopolamine models of spatial learning, and its synaptogenic effects in culture depend on hepatocyte growth factor (HGF) and its receptor c-Met.

A summary of published research for scientific reference. It is not medical advice and does not describe or endorse use in humans or animals. Findings from cell culture and animal models often do not carry over to other systems.

From angiotensin IV to a small peptidomimetic

Angiotensin IV, a fragment of angiotensin II, affects learning-related behavior in rodent models, but it breaks down quickly. Harding, Wright and colleagues built stabilized analogs of it. Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) was designed to resist peptidases and cross the blood–brain barrier.

Findings

McCoy and colleagues (Journal of Pharmacology and Experimental Therapeutics, 2013) tested dihexa in the Morris water maze in rats given scopolamine, and reported increased dendritic spine density in hippocampal neuron cultures.

Benoist and colleagues (2014) showed that these behavioral and synaptogenic effects depend on HGF/c-Met signaling. Dihexa binds HGF and promotes its dimerization, which potentiates c-Met activation.

Considerations

c-Met is a proto-oncogene, and HGF/c-Met signaling is involved in tumor growth and metastasis. Any research use of HGF potentiators should take this into account. The published literature remains small and comes mainly from the originating group.

References

  1. McCoy AT, Benoist CC, Wright JW, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141–154.
  2. Benoist CC, Kawas LH, Zhu M, et al. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther. 2014;351(2):390–402.