Origins
When was FOXO4-DRI created?
FOXO4-DRI is written backwards and built from mirror-image amino acids — which is why enzymes largely cannot read it.
The short answer
| Date | 2017 |
| Who | Peter de Keizer and colleagues |
| Where | Erasmus MC, Rotterdam, Netherlands |
| Origin | Designed, not found — it does not occur naturally in this form. |
Where it came from
The starting point is a stretch of the human protein FOXO4, the part that binds p53. A peptide copying that stretch would be expected to get in the way of the interaction, but a plain peptide copy would be taken apart quickly.
The answer used here is a retro-inverso design: reverse the order of the sequence, and build every residue as its D-enantiomer rather than the L-form life uses. The two changes cancel out geometrically — the side chains end up presented in roughly the arrangement of the original — while the backbone is one that protein-cutting enzymes, built around L-amino acids, handle very poorly.
The compound was published in Cell in 2017. Of all the compounds on this page it is the clearest demonstration of why the L and D distinction is worth understanding rather than skimming.
Why it is called that
FOXO4 for the parent protein. DRI is D-retro-inverso: D-amino acids, sequence reversed.
Where it stands now
FOXO4-DRI has not been approved as a medicine anywhere and has no international nonproprietary name.
What this page does not say
Nothing above is a statement about what FOXO4-DRI does in a body, and none of it is guidance on use. A compound’s history is a record of laboratories and dates; it is not evidence for anything, and the fact that a programme was looking for something is not a finding that it was found.
More on FOXO4-DRI
What is FOXO4-DRI? · The full timeline · FOXO4-DRI — sizes and prices
