title: Human ABC transporter ABCG2 in cancer chemotherapy: drug molecular design to circumvent multidrug resistance.
abstract: Human ATP-binding cassette (ABC) transporter ABCG2 (BCRP) is critically involved in multidrug resistance of human cancer. This transporter exhibits broad substrate specificity toward structurally diverse compounds, as do other ABC transporters, such as ABCB1 (P-glycoprotein/MDR1), ABCC1 (MRP1/GS-X pump), and ABCC2 (MRP2/cMOAT). To gain insight into the relationship between the molecular structure of compounds and the ABCG2-mediated transport activity, we have developed a high-speed screening method to analyze the substrate specificity of ABCG2. In addition, we have developed an algorithm that analyzes QSAR to evaluate ABCG2-drug interactions. This chapter presents our strategy of transport mechanism-based molecular design to circumvent multidrug resistance of cancer.
authors: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. Toshi-i@gsc.riken.jp
authors: Toshihisa
authors: T
authors: Ishikawa
authors: Hikaru
authors: H
authors: Saito
authors: Hiroyuki
authors: H
authors: Hirano
authors: Yutaka
authors: Y
authors: Inoue
authors: Yoji
authors: Y
authors: Ikegami
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D057166:High-Throughput Screening Assays; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship
chemical_list: C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D009363:Neoplasm Proteins