Dihexa
Angiotensin IV derived dipeptide mimetic, described as a hepatocyte growth factor (HGF) and c-Met potentiator
Status
Not approved
Not approved anywhere and never tested in a registered human trial. FDA states it has identified no human exposure data for dihexa acetate by any route. It sat in FDA's Category 2 of bulk substances that may present significant safety risks until the compounding nomination was withdrawn and the substance came off that list in April 2026, which does not by itself make compounding lawful; it is not on the 503A Bulks List and FDA has said the remaining peptides in this group will go before its compounding advisory committee at a later meeting.
Evidence
Animal data only
All efficacy claims come from rodent experiments by one laboratory, and the paper that established the proposed mechanism was retracted in 2025 while the paper that introduced dihexa carries a 2021 expression of concern.
In sport
WADAProhibited (WADA)
A small modified dipeptide built from a fragment of angiotensin IV, designed to survive digestion and reach the brain. It has never been tested in people and is sold only as a research chemical.
Structure
2 residuesPoint at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.
Sequence as text
hexanoyl-Y-I-6-aminohexanamide
What it is used for
- Memory and cognition in Alzheimer disease and age-related decline (claimed, unproven)
- Reversing scopolamine-induced memory deficits and promoting synapse formation in rodents (studied)
- Nerve repair and neuroprotection in animal models (studied)
How it works
Angiotensin IV fragments have long been reported to improve learning in rodents, but they break down quickly and do not cross the gut wall or blood-brain barrier. Dihexa adds a fatty acid at one end and an amide linker at the other to fix that. Its proposed action is to bind hepatocyte growth factor and enhance signalling through the c-Met receptor, which promotes formation of new synapses in the hippocampus. The key paper supporting that mechanism has since been retracted.
How strong the evidence is
Animal data only
McCoy and colleagues (2013) described dihexa as an orally active, brain-penetrant analogue that reversed scopolamine-induced deficits in the Morris water maze and improved performance in aged rats; that paper carries a 2021 expression of concern from the journal. Benoist and colleagues (2014) reported the hepatocyte growth factor and c-Met mechanism, and that paper was retracted in April 2025. Other rodent work reports effects on hair cell protection and on sciatic nerve repair. There are no human studies of any kind, and FDA found no human exposure data at all.
Risks and side effects
- No human data whatsoever: FDA found no exposure information for any route, so even basic tolerability is unknown
- The supporting literature is compromised, with one central paper retracted in 2025 and another under an expression of concern
- The proposed target, the hepatocyte growth factor and c-Met pathway, drives cell growth and is a well-known oncology target, so repeated stimulation carries an unquantified cancer risk
- Sold only as a research chemical, so identity, purity and sterility are unverified
- Prohibited in sport at all times under WADA class S0, and a substance said to potentiate hepatocyte growth factor may also fall under the growth factor class S2.3
Regulatory status
Status by country
| Jurisdiction | Status | Source |
|---|---|---|
| USUnited States | No authorised medicine | Source 3 |
| EUEuropean Union | No authorised medicine | Source 7 |
| UKUnited Kingdom | No authorised medicine | Source 8 |
| AUAustralia | No authorised medicine | Source 9 |
| CACanada | No authorised medicine | Source 10 |
Timeline
Sources
- 01Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents (expression of concern issued 2021)(opens the source in a new tab)
- 02The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system (retracted 2025)(opens the source in a new tab)
- 03Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks(opens the source in a new tab)
- 04FDA Announces Removal of 12 Peptides from Category 2 and Schedules PCAC Meetings(opens the source in a new tab)
- 05N-(1-Oxohexyl)-L-tyrosyl-N-(6-amino-6-oxohexyl)-L-isoleucinamide (dihexa), CID 129010512(opens the source in a new tab)
- 06The 2026 Prohibited List, International Standard(opens the source in a new tab)
- 07Find medicine: centrally authorised medicines(opens the source in a new tab)
- 08MHRA Products: active substances beginning with D(opens the source in a new tab)
- 09Australian Register of Therapeutic Goods (ARTG)(opens the source in a new tab)
- 10Drug Product Database online query(opens the source in a new tab)
Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.