Dihexa (PNB-0408) is a synthetic small molecule derived from angiotensin IV, developed at Washington State University by the Harding lab. It is a hepatocyte growth factor (HGF) mimetic that activates HGF/c-Met signaling in the brain, promoting synaptogenesis, neuroplasticity, and neuronal survival. Unlike large HGF proteins, Dihexa has good oral bioavailability and crosses the blood-brain barrier. In APP/PS1 Alzheimer's model mice, Dihexa activated the PI3K/AKT pathway, reduced neuroinflammation, and rescued cognitive impairment. It has also shown promise for peripheral nerve regeneration and protection against chemical ototoxicity. No human clinical trials exist.
Category: Nootropic / Cognitive. Evidence rating: F (anecdotal/unsupported).
Clinical status: Research-only / Preclinical. CAUTION: foundational paper retracted April 2025 for data fabrication.
Dihexa activates the hepatocyte growth factor receptor (c-Met) by binding to HGF molecules and dimerizing with endogenous HGF to form a functional ligand, producing more physiological signaling than direct c-Met agonists. This activates the PI3K/AKT signaling pathway, promoting neuronal survival,…
Research base: 0 registered clinical trials and 5 indexed publications reference Dihexa.
Safety considerations: No human safety data exists whatsoever; Short-duration animal studies report no apparent toxicity at research dosages; Potent HGF/c-Met activation raises theoretical oncological concerns (c-Met pathway involved in tumor progression).
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-07-05.
Related peptides: Noopept.
Compare: Dihexa vs Noopept.
No. As of 2026, there are no published human clinical trials for dihexa. All data is from animal studies (mouse Alzheimer's models, rat nerve repair) and cell culture experiments. No IND application has been filed with the FDA.
Unknown. There is zero human safety data. The HGF/c-Met pathway is involved in cancer progression, raising theoretical safety concerns with chronic use. Short animal studies showed no toxicity, but long-term effects are completely uncharacterized.
Animal studies used oral administration with confirmed blood-brain barrier penetration (Dihexa crosses the BBB). Oral (4-8 mg), topical (2-5 mg), and intranasal (1-3 mg) routes are discussed in research literature, but no human pharmacokinetic data exists.
Dihexa has a unique mechanism (HGF/c-Met pathway, PI3K/AKT signaling) distinct from racetams (cholinergic), selank/semax (GABAergic/BDNF), or modafinil (dopaminergic). Its theoretical potency is very high but supported only by preclinical data.
The HGF/c-Met signaling pathway is known to be involved in tumor growth, invasion, and metastasis. Activating this pathway chronically could theoretically promote cancer development, though this has not been studied with Dihexa specifically.