title: A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein.
abstract: P-glycoprotein (P-gp) functions as a drug efflux pump, mediating multidrug resistance and limiting the efficacy of many drugs. Clearly, identification of potential P-gp substrate liability early in the drug discovery process would be advantageous. We describe a multiple-pharmacophore model that can discriminate between substrates and nonsubstrates of P-gp with an accuracy of 63%. The application of this filter allows large virtual libraries to be screened efficiently for compounds less likely to be transported by P-gp.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Penzotti
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Lamb
authors.forename: Erik
authors.initials: E
authors.lastname: Evensen
authors.forename: Peter D J
authors.initials: PD
authors.lastname: Grootenhuis
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D006860:Hydrogen Bonding; D019469:Indinavir / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009529:Nicardipine / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019469:Indinavir; D009529:Nicardipine