Dihexa

Dihexa is a small compound designed as a metabolically stabilized, blood-brain-barrier-penetrant analog of angiotensin IV, an endogenous peptide fragment that acts on the brain AT4 receptor system. Preclinical work from its originating laboratory proposed that dihexa and related Nle1-angiotensin IV analogs potentiate hepatocyte growth factor (HGF) signaling through the c-Met receptor, promoting dendritic spine formation, hippocampal synaptogenesis, and improved performance in rodent memory tasks, independent of the classical renin-angiotensin system's blood-pressure effects.

All published dihexa data are preclinical (rodent and zebrafish models); no completed human trials, Investigational New Drug filing, or clinical dosing data have been identified as of 2026. Dihexa was first characterized as a procognitive/antidementia agent by McCoy et al. (J Pharmacol Exp Ther, 2013), from the Washington State University laboratory of Joseph Harding and Jay Wright, whose related angiotensin IV chemistry was later licensed to the spin-off company Athira Pharma. A 2021 Washington State University research-integrity investigation found that a co-author on this line of work (then a WSU doctoral student, later Athira's CEO) had altered or fabricated images in her dissertation and in several co-authored papers from the same program published 2011-2014; the university revoked her doctorate, and the closely related mechanistic follow-up paper (Benoist et al., J Pharmacol Exp Ther, 2014) was formally retracted in 2025 after the university confirmed falsified/fabricated figures. The original dihexa paper itself (McCoy et al., 2013) carries a published PubMed Notice of Concern (2021) rather than a retraction, but the episode substantially weakens confidence in the specific HGF/c-Met binding-affinity claims from this lab. Some independent support exists: a Chinese academic group unaffiliated with the Harding/Athira program (Sun et al., Brain Sciences, 2021) reported that dihexa improved spatial memory, increased synaptic markers, and reduced neuroinflammatory activation in an APP/PS1 Alzheimer's mouse model via PI3K/AKT signaling — encouraging, but still animal-only and not replicated by additional independent laboratories or in humans.

Educational overview only — no dosing instructions in the public hub.

No human clinical safety, tolerability, or pharmacokinetic data exist for dihexa at any dose, route, or duration. Because part of its foundational preclinical evidence base has been subject to a formal research-integrity investigation, one retraction, and one Notice of Concern, its mechanism and potency claims warrant added skepticism pending independent replication. As an unapproved, unregulated research chemical sold outside any pharmaceutical supply chain, material obtained online carries additional risk of misidentification, contamination, or incorrect concentration.

Any dihexa research sample should carry an independent third-party Certificate of Analysis confirming identity and purity by HPLC plus quantification by mass spectrometry (MS); given the compound's obscure supply chain, lack of pharmaceutical-grade manufacturing, and the integrity concerns affecting parts of the founding literature, lot-specific verification is essential rather than optional.

Research Use Only (RUO) in the US, EU, and UK; not approved as a drug by the FDA, EMA, or MHRA. No Investigational New Drug application or registered human trial for dihexa itself has been identified. Where sold, it is offered strictly as an unregulated research chemical, outside any medical or regulatory oversight.