Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39663371.
- Also identified by DOI 10.1038/s41587-024-02503-w and PMC identifier 12611778.
- Licence recorded as CC BY-NC-ND.
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Abstract
Hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.
Medical subject headings
- Intestinal Mucosa
- Hypoxia-Inducible Factor-Proline Dioxygenases
- Artificial Intelligence
- Prolyl-Hydroxylase Inhibitors