4NY4

Crystal structure of CYP3A4 in complex with an inhibitor

4NY4 の概要

• エントリーDOI: 10.2210/pdb4ny4/pdb
• 関連するPDBエントリー: 4NZ2
• 分子名称: Cytochrome P450 3A4, PROTOPORPHYRIN IX CONTAINING FE, (8R)-3,3-difluoro-8-[4-fluoro-3-(pyridin-3-yl)phenyl]-8-(4-methoxy-3-methylphenyl)-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (3 entities in total)
• 機能のキーワード: cytochrome p-450, cyp3a4, inhibitor, structure-based drug design, drug metabolism, monooxygenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass membrane protein: P08684
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56432.25

構造登録者

Branden, G.,Sjogren, T.,Xue, Y. (登録日: 2013-12-10, 公開日: 2014-08-13, 最終更新日: 2024-02-28)

主引用文献

Branden, G.,Sjogren, T.,Schnecke, V.,Xue, Y.
Structure-based ligand design to overcome CYP inhibition in drug discovery projects.
Drug Discov Today, 19:905-911, 2014

PubMed Abstract: Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects.

PubMed: 24642031
DOI: 10.1016/j.drudis.2014.03.012

実験手法

X-RAY DIFFRACTION (2.95 Å)