9IZLSummary for 9IZL
| Entry DOI | 10.2210/pdb9izl/pdb |
| Descriptor | Pantetheinase, 8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(3~{S})-3-oxidanylpyrrolidin-1-yl]-1,3-thiazol-5-yl]methanone (3 entities in total) |
| Functional Keywords | inhibitor, complex, hvanin-1, hydrolase, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 103846.55 |
| Authors | |
| Primary citation | Xie, T.,Cao, G.Y.,Zhang, S.,Li, M.K.,Jin, X.,Liu, L.,Wang, G.,Zhen, L. Discovery of Thiazole Carboxamides as Novel Vanin-1 Inhibitors for Inflammatory Bowel Disease Treatment. J.Med.Chem., 67:20372-20398, 2024 Cited by PubMed Abstract: Inflammatory bowel disease (IBD) is a clinically heterogeneous disease demanding more therapeutic targets and intervention strategies. Vanin-1, an oxidative stress-regulating protein, has emerged as a promising target for alleviating inflammation and oxidative stress. In this study, a series of thiazole carboxamide derivatives as vanin-1 inhibitors were designed and synthesized. The preferred compound, , demonstrated potent inhibition against vanin-1 at the protein, HT-29 cell, and tissue levels, whose binding mode with the target was confirmed via the cocrystal structure. achieved a high bioavailability of 81% in rats, accompanied by concentration-dependent inhibition of serum vanin-1. In a DSS-induced mouse colitis model, exhibited potent anti-inflammatory and antioxidant activities, repressing the inflammatory factor expressions and myeloperoxidase activity, elevating the colonic glutathione reserve, and restoring the intestinal barrier. Collectively, these findings depict the discovery of a potent vanin-1 inhibitor, providing an opportunity for further drug candidate development for treating IBD. PubMed: 39514323DOI: 10.1021/acs.jmedchem.4c01838 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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