6DUP

CRYSTAL STRUCTURE OF PXR IN COMPLEX WITH COMPOUND 7

6DUP の概要

• エントリーDOI: 10.2210/pdb6dup/pdb
• 分子名称: 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)
• 機能のキーワード: pxr, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78756.41

構造登録者

Chen, X.,Zhang, Y.,Mclean, L.R. (登録日: 2018-06-21, 公開日: 2018-08-29, 最終更新日: 2024-03-13)

主引用文献

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

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: 30146095
DOI: 10.1016/j.bmcl.2018.08.022

実験手法

X-RAY DIFFRACTION (2.3 Å)