Dihexa

Dihexa (N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide)

Evidence & Status

  • Preliminary / Experimental
  • Preliminary

At a Glance

A synthetic peptide designed to penetrate the blood-brain barrier and activate the HGF/c-Met signaling pathway, which promotes synapse formation between neurons. Studied in the context of Alzheimer's disease research and cognitive function.

Plain English

Researchers study Dihexa because it was specifically designed to activate a signaling pathway — involving hepatocyte growth factor and its receptor c-Met — that promotes the formation of new connections between neurons. Scientists are interested in whether supporting synaptogenesis through this pathway could be relevant to cognitive decline in aging or neurodegenerative disease. Research is currently limited to animal models and cell studies, with no human clinical trial data yet available, placing it in an early exploratory stage.

Overview

A synthetic peptidomimetic developed at Washington State University (Harding laboratory) for Alzheimer's research. Crosses the blood-brain barrier readily and promotes synaptogenesis by activating HGF/c-Met signaling. Reported in preclinical studies to have dramatically greater potency than BDNF in synaptic growth assays; this comparison has not been established in human studies. Human pharmacokinetic half-life has not been established. No human clinical trials have been conducted.

Research Summary

Dihexa is among the most research-limited compounds in this database. All published evidence derives from a small number of preclinical studies by the Harding laboratory at Washington State University. Two verified publications (Benoist et al., 2014; McCoy et al., 2013) demonstrate synaptogenesis and procognitive effects in rodent models dependent on HGF/c-Met pathway activation. Potency comparisons to BDNF are reported in preclinical publications but have not been validated in human studies; the specific magnitude of potency difference cited in earlier versions of this record is not independently confirmed from the verified sources. A preclinical study in the APP/PS1 Alzheimer's mouse model demonstrated cognitive rescue and memory recovery via PI3K/AKT pathway activation (Sun et al., 2021); this evidence is animal-model only and has not been replicated in human studies. The compound has never been studied in humans. Human pharmacokinetic half-life has not been established; the previously stored estimate of ~25 days has no authorized primary source and has been removed. The previously stored PubMed identifiers (PMID 23415862 and PMID 23541167) were confirmed as entity mismatches and have been removed. Known pro-oncogenic potential of HGF/c-Met signaling adds theoretical safety concern. Evidence remains preliminary.

Research Areas

  • Alzheimer's disease & dementia
  • Cognitive enhancement
  • Synaptogenesis
  • Memory consolidation
  • HGF/c-Met pathway

Safety & Risks

Serious Risks

  • Extremely long half-life makes overconsumption difficult to reverse; pro-oncogenic via HGF/c-Met pathway (c-Met is a known oncogene); insufficient human safety data

Reported Side Effects

  • Currently unknown in humans; fatigue reported anecdotally
  • Potential for excessive excitatory signaling (theoretical)
United States
Research only (no scheduled status; unregulated gray area)
United Kingdom
Research only
Australia
Research only
Canada
Research only

Citations & Sources