title: Drug-drug interation prediction between ketoconazole and anti-liver cancer drug Gomisin G.
abstract: BACKGROUND
  Gomisin G, isolated from herb Schisandra chinensis, exhibits anti-tumor activities. Therefore, Gomisin G is a drug candidate for anti-liver cancer therapy.
  
  
  OBJECTIVE
  To predict the metabolic behavior and metabolism-based drug-drug interaction of gomisin G.
  
  
  METHODS
  Molecular docking method was used. The crystal structure of CYP3A4 with the ligand ketoconazole was chosen from protein data bank (http://www.rcsb.org/pdb). Chemdraw software was used to draw the two-dimensional structure of gomisin G with standard bond lengths and angles.
  
  
  RESULTS
  Gomisin G can be well docked into the activity site of CYP3A4, and distance between gomisin G the heme active site was 2.75 Å. To evaluate whether the inhibitors of CYP3A4 can affect the metabolism of gomisin G, co-docking of gomisin G and ketoconazole was further performed. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between gomisin G and activity center of CYP3A4, indicating the easy influence of CYP3A4's strong inhibitor towards the metabolism of gomisin G.
  
  
  CONCLUSIONS
  Gomisin G is a good substrate of CYP3A4, and CYP3A4 inhibitors easily affect the metabolism of Gomisin G.
authors.affiliation: Department of Hepatobiliary Surgery, Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Xiaoyang
authors.affiliation: Laboratory of Pharmacology, Department of Pharmacy, Jinan Military General Hospital, Jinan 250031, P.R. China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chenming
authors.affiliation: Department of General Surgery, No. 1 Hospital of People's Liberation Army, Lanzhou 730030, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chengqing
authors.affiliation: Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D034242:Cyclooctanes / Q000737:chemistry / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology*; D004149:Dioxoles / Q000737:chemistry / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry; D032141:Schisandra / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D034242:Cyclooctanes; D065692:Cytochrome P-450 CYP3A Inhibitors; D004149:Dioxoles; D017705:Lignans; D010936:Plant Extracts; C034557:schizandrer A; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole
keywords: CYP3A4; Gomisin G; molecular docking