title: QSAR analysis and molecular modeling of ABCG2-specific inhibitors.
abstract: In addition to its critical role is controlling drug availability and protecting sensitive organs and stem cells through cellular detoxification, breast cancer resistance protein (BCRP/ABCG2) plays an important role in cancer cell resistance to chemotherapy, together with P-glycoprotein/ABCB1. A main approach to abolish multidrug resistance is to find out specific inhibitors of the drug-efflux activity, able to chemosensitize cancer cell proliferation. Many efforts have been primarily focused on ABCB1, discovered thirty years ago, whereas very few studies have concerned ABCG2, identified much more recently. This review describes the main types of inhibitors presently known for ABCG2, and how quantitative structure-activity relationship analysis among series of compounds may lead to build up molecular models and pharmacophores allowing to design lead inhibitors as future candidates for clinical trials. A special attention is drawn on flavonoids which constitute a structurally-diverse class of compounds, well suited to identify potent ABCG2-specific inhibitors.
authors.affiliation: Département de Pharmacochimie Moléculaire, UMR 5063. ICMG-FR 2607-Université Joseph Fourier Grenoble I, 470 rue de la Chimie, 38240 St Martin d'Hères, France.
authors.forename: E
authors.initials: E
authors.lastname: Nicolle
authors.forename: A
authors.initials: A
authors.lastname: Boumendjel
authors.forename: S
authors.initials: S
authors.lastname: Macalou
authors.forename: E
authors.initials: E
authors.lastname: Genoux
authors.forename: A
authors.initials: A
authors.lastname: Ahmed-Belkacem
authors.forename: P-A
authors.initials: PA
authors.lastname: Carrupt
authors.forename: A
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000502:physiology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins