Adamax (Dihexa)

What Is Adamax (Dihexa)?

Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide, also called PNB-0408) is a small, orally bioavailable, blood-brain-barrier-penetrant analogue of angiotensin IV developed in the laboratory of Joseph Harding and John McCoy at Washington State University in the early 2010s. Angiotensin IV was already known to enhance memory in animal models but was peptidase-sensitive and poorly bioavailable. The Harding and McCoy team attached a hexanoic acid cap to the N-terminus and a 6-aminohexanoic acid amide to the C-terminus, which stabilises the molecule against peptidases and makes it small enough to cross the blood-brain barrier.

Mechanistically, Dihexa is best characterised as a hepatocyte growth factor (HGF) potentiator: it binds HGF directly and stabilises the HGF-c-Met receptor interaction, amplifying signalling through the c-Met tyrosine kinase pathway. In the WSU rat work, the downstream consequence in the central nervous system was rapid induction of dendritic arborisation and synaptogenesis in the hippocampus, with picomolar potency in dissociated hippocampal neuron cultures and reversal of scopolamine-induced memory deficits. The often-quoted comparison to BDNF originates in the Harding laboratory's spinogenesis assays comparing molar potency in dendritic spine formation, not in any direct functional head-to-head.

The same c-Met pathway is a well-characterised oncogenic signal, dysregulated or overexpressed in lung, gastric, hepatocellular, renal, and glioblastoma tumours, and HGF/c-Met is an active target of anti-cancer drug development. No human data exist for Dihexa in either direction, and the theoretical oncogenic mechanism is the central caveat in every published commentary.