Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor

ABSTRACT: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) inhibitors have been approved for treating renal anemia, yet have failed clinical testing for inflammatory bowel disease (IBD) due to lack of efficacy. We use a multimodel multimodal generative AI platform to design an orally gut-restricted selective PHD1/2 inhibitor, which exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colon

SUBMITTER: Chenxi Xu  

LAB HEAD: Yanyun Fu

PROVIDER: PXD057486 | Pride | 2024-12-12

REPOSITORIES: Pride