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Eur J Drug Metab Pharmacokinet. 2015 Jun;40(2):235-8. doi: 10.1007/s13318-014-0201-1. Epub 2014 Apr 23.

Molecular docking to understand the metabolic behavior of GNF-351 by CYP3A4 and its potential drug-drug interaction with ketoconazole.

Author information

1
Department of Dermatology and Venereology, Tangdu Hospital, The Fourth Military Medical University, No.569 Xinsi Road, Xi'an, 710038, China, kaixinshike313@163.com.

Abstract

GNF-351 is a candidate drug used to treat some diseases through antagonizing aryl hydrocarbon receptor. In the present study, molecular docking method was employed to understand the interaction between ketoconazole and GNF-351. The structure of cytochrome P450 (CYP) 3A4 was obtained from protein data bank, and 2-dimensional structure of GNF-351 with standard bond lengths and angles was drawn using chemdraw software. 30 possible binding orientations was generated and docked into the X-ray crystallographic structure of human CYP3A4. The predicted binding mode of GNF-351 into CYP3A4 appeared to adopt an orientation with interactions between their flat aromatic rings and Phe 302 and Phe 304. The comparison for the binding of GNF-351 and ketoconazole into the activity cavity indicated that they exhibited similar distance towards heme, indicating the potential interaction between GNF-351 and ketoconazole. These data remind us the necessary monitoring when future utilization between GNF-351 and ketoconazole.

PMID:
24756863
DOI:
10.1007/s13318-014-0201-1
[Indexed for MEDLINE]

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