Most compound profiles summarize what a literature found. This one is about how to read a literature when part of it has been withdrawn. Dihexa is a useful worked example because the notices are public, the paper count is small, and secondary sources may not mention the notices.
What Dihexa Is
Dihexa is a chemically modified, short peptide-like compound: N-hexanoic-Tyr-Ile-(6)aminohexanoic amide. McCoy and colleagues described it in 2013 as an angiotensin IV (AngIV)-derived analog, built from the three N-terminal residues of an AngIV analog (Nle-Tyr-Ile) with modifications intended to improve stability and barrier permeability. It is not a naturally occurring peptide, and its name does not describe a sequence in the usual sense. See What Peptide Names Mean.
The Record, in Order
| Year | Item | Status |
|---|---|---|
| 2012–2013 | McCoy et al., J Pharmacol Exp Ther: evaluation of metabolically stabilized AngIV analogs, with dihexa as the lead compound, in rodent behavioral and synaptic models | Carries a 2021 Expression of Concern |
| 2012 | Kawas et al., J Pharmacol Exp Ther: AngIV analogs as modifiers of the HGF/Met system | Retracted; notice published April 2025 |
| 2014 | Benoist et al., J Pharmacol Exp Ther: AngIV-derived peptides and the HGF/c-Met system | Retracted; notice published April 2025 |
| 2021 | Sun et al., Brain Sciences: dihexa in a transgenic mouse model | Published; independent group; declares no conflict of interest |
The PubMed records for the 2025 retraction notices identify the retracted papers and their authors but do not carry the reasons. Read the full notices on the journal's site for the stated reasons. Do not infer them.
Questions to Ask
- Which papers did the retractions remove, and what did they support? Two of the retracted papers address the HGF/Met pathway, which the group used to explain how AngIV analogs act. A reader should check whether a later claim cites those papers for its mechanism.
- What does an expression of concern mean? It is an editor's flag that a paper's reliability is under question, short of a retraction. The 2013 paper's expression of concern appeared in September 2021. Papers that rely on that paper's data should be read with that flag in mind.
- Who are the authors? The 2013 paper and the two retracted papers share authors from the same group. Independent replication is a separate matter.
- What is independent? The 2021 Brain Sciences paper is from a different institution and reports effects in the APP/PS1 mouse model, including changes in inflammation markers and the PI3K/AKT pathway. It is a single mouse study. It does not by itself establish the mechanism described in the withdrawn papers.
- What model was used? Everything above is in rodents or cultured cells. See Dish, Mouse or Human? Reading the Model Behind a Peptide Study.
For a general method, see When a Paper Is Retracted.
What This Means for a Lab
- Look up every cited paper in PubMed and the journal's site before relying on it.
- Regard secondary summaries, forum posts and vendor pages as pointers, not evidence.
- Record the status of each paper you cite: current, expression of concern, corrected or retracted.
- Report the status in your methods or lab notes, so a later reader can see the state of the record on your date of reading.
If You Source This Compound for Research
- Request an analytical report that confirms the structure by mass and gives HPLC purity. Because dihexa is a modified, non-standard structure, ask for the structure the lab tested, not only a name.
- Store lyophilized material cold, dry and away from light. See Storing Lyophilized Peptides in the Lab and How to Read a Peptide Analytical Report.
FAQ
Is dihexa a peptide? It is a peptide-like compound with an N-terminal hexanoyl group and a C-terminal amide. The 2013 paper calls it an AngIV analog.
Does a retraction of related papers mean the compound's whole record is invalid? No. It means each retracted paper no longer counts as evidence. The rest of the record is judged on its own.
What should I cite? Cite primary papers and state their status, instead of repeating a secondary summary.
Sources
- McCoy AT et al. J Pharmacol Exp Ther, 2013. PubMed 23055539: https://pubmed.ncbi.nlm.nih.gov/23055539/
- Sun X et al. Brain Sciences, 2021. PubMed 34827486: https://pubmed.ncbi.nlm.nih.gov/34827486/
- Kawas LH et al. Retraction notice, J Pharmacol Exp Ther, 2025. PubMed 40312092: https://pubmed.ncbi.nlm.nih.gov/40312092/
- Benoist CC et al. Retraction notice, J Pharmacol Exp Ther, 2025. PubMed 40312093: https://pubmed.ncbi.nlm.nih.gov/40312093/
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