6DUP
CRYSTAL STRUCTURE OF PXR IN COMPLEX WITH COMPOUND 7
Summary for 6DUP
| Entry DOI | 10.2210/pdb6dup/pdb |
| Descriptor | Nuclear receptor subfamily 1 group I member 2, (2S)-2-({[3'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]oxy}methyl)-2,3-dihydro-7H-[1,3]oxazolo[3,2-a]pyrimidin-7-one (3 entities in total) |
| Functional Keywords | pxr, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 78756.41 |
| Authors | Chen, X.,Zhang, Y.,Mclean, L.R. (deposition date: 2018-06-21, release date: 2018-08-29, Last modification date: 2024-03-13) |
| Primary citation | Vaz, R.J.,Li, Y.,Chellaraj, V.,Reiling, S.,Kuntzweiler, T.,Yang, D.,Shen, H.,Batchelor, J.D.,Zhang, Y.,Chen, X.,McLean, L.R.,Kosley Jr., R. Amelioration of PXR-mediated CYP3A4 induction by mGluR2 modulators. Bioorg. Med. Chem. Lett., 28:3194-3196, 2018 Cited by PubMed Abstract: This work describes the rational amelioration of Cytochrome P450 4/5 (CYP3A4/5) induction through the Pregnane-X Receptor (PXR) pathway in a series of compounds that modulate the metabotropic glutamate Receptor 2 (mGluR2) via an allosteric mechanism. The compounds were initially shown to induce CYP3A4/5 via the gold-standard induction assay measured in primary human hepatocytes. This was followed up by testing the compounds in a PXR assay which correlated well with the assay in primary cells. Further, one of the compounds was crystallized with PXR (pdb code 6DUP). Analysis of this co-crystal structure, together with previously published PXR co-crystal structures, lead to modification ideas. The compounds synthesized based on these ideas were shown not to be CYP3A4/5 inducers. The mGluR2 activity of the resulting compounds was maintained. PubMed: 30146095DOI: 10.1016/j.bmcl.2018.08.022 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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