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

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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.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (No. 30900772).

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Authors and Affiliations

  1. Department of Dermatology and Venereology, Tangdu Hospital, The Fourth Military Medical University, No.569 Xinsi Road, Xi’an, 710038, China

    Tao Liu & YanGuo Zhang

  2. Department of Dermatology and Venereology, Zhengzhou Children’s Hospital, No. 255 Gangdu Street, Zhengzhou, 450053, China

    Ge Qian

  3. Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, No.17 Changle Road, Xi’an, 710032, China

    WenTing Wang

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  1. Tao Liu
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  2. Ge Qian
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  3. WenTing Wang
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  4. YanGuo Zhang
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Corresponding author

Correspondence to Tao Liu.

Additional information

T. Liu and G. Qian have equally contributed to this work.

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Liu, T., Qian, G., Wang, W. et al. Molecular docking to understand the metabolic behavior of GNF-351 by CYP3A4 and its potential drug–drug interaction with ketoconazole. Eur J Drug Metab Pharmacokinet 40, 235–238 (2015). https://doi.org/10.1007/s13318-014-0201-1

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  • DOI: https://doi.org/10.1007/s13318-014-0201-1

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