Molecular docking to understand the metabolic behavior of GNF-351 by CYP3A4 and its potential drug-drug interaction with ketoconazole.
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.
Department of Dermatology and Venereology, Tangdu Hospital, The Fourth Military Medical University, No.569 Xinsi Road, Xi'an, 710038, China, kaixinshike313@163.com.
Tao
T
Liu
Ge
G
Qian
WenTing
W
Wang
YanGuo
Y
Zhang
D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D004347:Drug Interactions; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007654:Ketoconazole / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011687:Purines / Q000737:chemistry / Q000378:metabolism*
D007211:Indoles; C560625:N-(2-(3H-indol-3-yl)ethyl)-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-amine; D011687:Purines; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole