8Y0V

HIF prolyl hydroxylase 2 in complex with inhibitor

This is a non-PDB format compatible entry.

Summary for 8Y0V

• Entry DOI: 10.2210/pdb8y0v/pdb
• Descriptor: Egl nine homolog 1, ~{tert}-butyl 4-[6-[(6-cyanopyridin-3-yl)methylcarbamoyl]-5-oxidanyl-1,7-naphthyridin-2-yl]piperazine-1-carboxylate, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: inhibitor, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 28069.78

Authors

Ding, X.,Fan, Y. (deposition date: 2024-01-23, release date: 2024-12-18, Last modification date: 2024-12-25)

Primary citation

Fu, Y.,Ding, X.,Zhang, M.,Feng, C.,Yan, Z.,Wang, F.,Xu, J.,Lin, X.,Ding, X.,Wang, L.,Fan, Y.,Li, T.,Yin, Y.,Liang, X.,Xu, C.,Chen, S.,Pulous, F.E.,Gennert, D.,Pun, F.W.,Kamya, P.,Ren, F.,Aliper, A.,Zhavoronkov, A.
Intestinal mucosal barrier repair and immune regulation with an AI-developed gut-restricted PHD inhibitor.
Nat.Biotechnol., 2024

PubMed 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.

PubMed: 39663371
DOI: 10.1038/s41587-024-02503-w

Experimental method

X-RAY DIFFRACTION (2.5 Å)