Dihexa — 10mg

Dihexa (N-hexanoic-Tyr-Ile-(6)aminohexanoic amide) is a hexapeptide derivative of angiotensin IV developed at Washington State University by the Harding and Wright laboratories. Its development began with the observation that angiotensin IV, a metabolic product of the renin-angiotensin system, produces cognitive enhancement effects in animal models of learning and memory. Structural optimization to improve metabolic stability, blood-brain barrier penetration, and oral bioavailability produced Dihexa as the lead candidate from this program, with pharmacological properties substantially distinct from its angiotensin-family origin.

The compound's primary mechanism involves activation of hepatocyte growth factor (HGF) / c-Met receptor signaling in the central nervous system. HGF is a potent synaptogenic factor that drives dendritic spine formation, synapse maturation, and neuronal survival, but does not cross the blood-brain barrier effectively as a large protein — making it difficult to use therapeutically despite its biological activity. Dihexa functions as a small-molecule HGF activator that potentiates c-Met signaling and is orally bioavailable with BBB penetration via transcellular transport. Published preclinical studies report dendritic spine formation potency in the range of 10⁷-fold greater than BDNF on a molar basis — a figure that has generated both intense research interest and appropriate skepticism regarding reproducibility and translation to clinical outcomes.

Research applications center on neurodegenerative disease models, particularly Alzheimer's disease, where cognitive improvements and reductions in amyloid-associated pathology have been reported in animal protocols. Parallel lines of investigation have examined Dihexa in stroke recovery, traumatic brain injury, and age-related cognitive decline models. The compound remains in preclinical research without published human clinical trials, and its characterization is ongoing — particularly with respect to long-term safety, tissue distribution, and dose-response in chronic administration protocols. Its combination of oral bioavailability, BBB penetration, and HGF/c-Met selectivity makes it a mechanistically attractive research tool, but claims of unprecedented synaptogenic potency warrant cautious interpretation pending independent replication and human data.