Dihexa

Dihexa (developmental code PNB-0408) is a small peptidomimetic derived from angiotensin IV — chemically N-hexanoyl-Tyr-Ile-(6)-aminohexanoic amide. It was developed at Washington State University (Joseph Harding's group) to overcome the rapid degradation and poor brain penetration of native angiotensin IV, and is researched for cognition via a distinctive growth-factor mechanism. It is not approved and is supplied for research use only.

What is Dihexa and how does its HGF/c-Met mechanism work?

In preclinical cell-based studies, Dihexa is proposed to bind hepatocyte growth factor (HGF) and potentiate HGF/c-Met signaling — a pathway tied to neuronal survival, axonal growth, and synapse formation — driving hippocampal spinogenesis and synaptogenesis in preclinical models. This growth-factor mechanism sets it apart from cognitive compounds that act on BDNF/ACTH pathways (like Noopept) or cell-adhesion signaling (like FGL).

Source: The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system, Benoist C.C., et al. (optional, non-blocking: complete list), J Pharmacol Exp Ther (optional, non-blocking follow-up: confirm venue/vol), 2014

Why was Dihexa engineered from angiotensin IV?

Native angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) influences memory but degrades rapidly and penetrates the brain poorly; Dihexa's N-terminal hexanoylation and C-terminal amidation confer peptidase resistance and lipophilicity, improving blood-brain-barrier passage and enabling oral activity in preclinical models. That pharmacokinetic engineering is central to its identity as a research tool.

What does the research on Dihexa show?

Evidence is preclinical: cell-culture, ex vivo hippocampal-slice, and animal studies show HGF/c-Met potentiation, increased dendritic spine density, and synaptogenesis; the foundational mechanistic work was published in the early 2010s. There are no controlled human efficacy trials.

Evidence level: preclinical only

What are the safety and regulatory considerations?

Dihexa is not approved for human use and has no established human safety profile; note that HGF/c-Met is also a pathway implicated in cancer biology, which is a reason for caution with a growth-factor-potentiating compound. As of August 2026 no regulator has approved Dihexa for any use. Dihexa acetate is not on the FDA's active Category 2 "do-not-compound" list; its compounding nomination was withdrawn by the nominator, and the FDA has slated dihexa acetate for Pharmacy Compounding Advisory Committee consideration before the end of February 2027 — an advisory step that does not, by itself, make it an approved or lawfully compounded drug. See the legal status guide.

Source: FDA Pharmacy Compounding Advisory Committee meeting scheduled before end of February 2027 — 503A bulks consideration (LL-37, dihexa acetate, injectable GHK-Cu, PEG-MGF, melanotan II), FDA

Why does vendor verification matter, and how does Peptigrity verify?

As a potent, structurally specific research peptidomimetic, Dihexa needs mass-spec identity and HPLC purity confirmation to ensure a vial contains the correct compound at the labeled amount. Peptigrity collects independent third-party Certificates of Analysis for Dihexa from shops' official channels and verifies each for authenticity before publishing. Because shops choose which COAs to publish, results reflect the batches shops have made public rather than every production batch — a selection bias we state openly. A community-funded Testing Grant to purchase and test vials anonymously is in development. Tests in the database come from independent labs such as Janoshik Analytical, Freedom Diagnostics, and Chromate. See how to read lab results.

Educational information only; not medical advice. Dihexa is not approved for human use. Consult a qualified healthcare provider. Peptigrity does not sell, endorse, or recommend products or vendors.

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