4NY4

Crystal structure of CYP3A4 in complex with an inhibitor

Summary for 4NY4

• Entry DOI: 10.2210/pdb4ny4/pdb
• Related: 4NZ2
• Descriptor: 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)
• Functional Keywords: cytochrome p-450, cyp3a4, inhibitor, structure-based drug design, drug metabolism, monooxygenase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Single-pass membrane protein: P08684
• Total number of polymer chains: 1
• Total formula weight: 56432.25

Authors

Branden, G.,Sjogren, T.,Xue, Y. (deposition date: 2013-12-10, release date: 2014-08-13, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)