title: Predicting substrates of the human breast cancer resistance protein using a support vector machine method.
abstract: BACKGROUND
  Human breast cancer resistance protein (BCRP) is an ATP-binding cassette (ABC) efflux transporter that confers multidrug resistance in cancers and also plays an important role in the absorption, distribution and elimination of drugs. Prediction as to if drugs or new molecular entities are BCRP substrates should afford a cost-effective means that can help evaluate the pharmacokinetic properties, efficacy, and safety of these drugs or drug candidates. At present, limited studies have been done to develop in silico prediction models for BCRP substrates. In this study, we developed support vector machine (SVM) models to predict wild-type BCRP substrates based on a total of 263 known BCRP substrates and non-substrates collected from literature. The final SVM model was integrated to a free web server.
  
  
  RESULTS
  We showed that the final SVM model had an overall prediction accuracy of ~73% for an independent external validation data set of 40 compounds. The prediction accuracy for wild-type BCRP substrates was ~76%, which is higher than that for non-substrates. The free web server (http://bcrp.althotas.com) allows the users to predict whether a query compound is a wild-type BCRP substrate and calculate its physicochemical properties such as molecular weight, logP value, and polarizability.
  
  
  CONCLUSIONS
  We have developed an SVM prediction model for wild-type BCRP substrates based on a relatively large number of known wild-type BCRP substrates and non-substrates. This model may prove valuable for screening substrates and non-substrates of BCRP, a clinically important ABC efflux drug transporter.
authors.affiliation: Virtua Drug Ltd., Csalogany Street 4, Budapest H-1015, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Hazai
authors.forename: Istvan
authors.initials: I
authors.lastname: Hazai
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ragueneau-Majlessi
authors.forename: Sophie P
authors.initials: SP
authors.lastname: Chung
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bikadi
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Mao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy; D004341:Drug Evaluation; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D060388:Support Vector Machine
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins