What Is Dihexa?
Dihexa is a synthetic small-molecule peptide analog derived from Angiotensin IV, designed to penetrate the blood-brain barrier and potently activate the HGF (Hepatocyte Growth Factor) / c-Met signaling pathway in the brain. Developed at Washington State University by Joseph Harding et al., it is reported to be approximately 7 orders of magnitude more potent than BDNF at promoting hippocampal synaptogenesis — potentially making it the most powerful synaptogenic compound known.
HGF/c-Met Pathway in Neuroplasticity
HGF acts as a potent neurotrophin in the brain, binding c-Met receptor tyrosine kinase to promote neuron survival, axon sprouting, and synaptogenesis. In the hippocampus, HGF/c-Met signaling is critical for memory consolidation and synaptic plasticity. Dihexa potentiates HGF binding to c-Met with extraordinary potency, dramatically amplifying this neuroprotective and neurogenic signaling cascade.
Cognitive Enhancement and BBB Penetration
In animal studies, Dihexa administration produced dramatic improvements in object recognition memory, spatial memory, and problem-solving tasks — with effects at picomolar concentrations. In aged animals with cognitive deficits, Dihexa restored performance to levels comparable to young animals. Unlike most peptides and proteins, Dihexa's modified structure allows it to cross the blood-brain barrier following systemic administration — oral, intranasal, or subcutaneous — enabling CNS delivery without intrathecal injection.
Quick Reference
Member reference tables summarize the compound's research parameters.
Research Indications
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below), not a personal dosing recommendation.
This member section describes parameters reported in the research literature.
Peptide Interactions
This member section summarizes reported compound interactions and evidence limitations.
Reported Research Time Points
This member section summarizes reported research time points.
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
This member section discusses research safety considerations and uncertainties.
Quality Indicators
Research Citations
- AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
Sun X, Deng Y, Li W, et al., 2021, International Journal of Molecular Sciences - The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system
Benoist CC, Kawas LH, Zhu M, et al., 2014, Journal of Pharmacology and Experimental Therapeutics - Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents
McCoy AT, Benoist CC, Wright JW, et al., 2013, Journal of Pharmacology and Experimental Therapeutics - The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases
Wright JW, Kawas LH, Harding JW, 2015, Progress in Neurobiology - Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies
Ho JK, Nation DA, 2018, Neuroscience & Biobehavioral Reviews - Dimeric DOTA-alpha-melanocyte-stimulating hormone analogs: synthesis and in vivo characteristics of radiopeptides with high in vitro activity
Bapst JP, Froidevaux S, Calame M, 2007, J Recept Signal Transduct Res