title: Pharmacoinformatic approaches to design natural product type ligands of ABC-transporters.
abstract: ABC-transporter have been recognized as being responsible for multiple drug resistance in tumor therapy, for decreased brain uptake and low oral bioavailability of drug candidates, and for drug-drug interactions and drug induced cholestasis. P-glycoprotein (ABCB1), the paradigm protein in the field, is mainly effluxing natural product toxins and shows very broad substrate specificity. Within this article we will highlight SAR and QSAR approaches for designing natural product type inhibitors of ABCB1 and related proteins as well as in silico strategies to predict ABCB1 substrates and inhibitors in order to design out undesirable drug/protein interaction.
authors.affiliation: Department of Medicinal Chemistry, University of Vienna, Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Klepsch
authors.forename: I
authors.initials: I
authors.lastname: Jabeen
authors.forename: P
authors.initials: P
authors.lastname: Chiba
authors.forename: G F
authors.initials: GF
authors.lastname: Ecker
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005419:Flavonoids / Q000737:chemistry; D008024:Ligands; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry; D013256:Steroids / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D001688:Biological Products; D005419:Flavonoids; D008024:Ligands; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012717:Sesquiterpenes; D013256:Steroids