title: Prediction of drug-target interactions and drug repositioning via network-based inference.
abstract: Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Feixiong
authors.initials: F
authors.lastname: Cheng
authors.forename: Chuang
authors.initials: C
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Lu
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: Guixia
authors.initials: G
authors.lastname: Liu
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001665:Binding Sites; D030562:Databases, Protein; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins