title: Rational design of platinum(IV) compounds to overcome glutathione-S-transferase mediated drug resistance.
abstract: A rationally designed Pt(IV) anticancer compound is described, employing the novel concept of tethering an inhibitor of glutathione-S-transferase, an enzyme associated with Pt-based drug-resistance, to cisplatin. Its enzyme inhibition activity, investigated using spectrophotometric and mass spectrometry-based techniques, and cytotoxic profile in resistant cancer cells are described.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, EPFL-BCH, CH 1015 Lausanne, Switzerland.
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
authors.forename: Isam
authors.initials: I
authors.lastname: Khalaila
authors.forename: Claire S
authors.initials: CS
authors.lastname: Allardyce
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeanneret
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009944:Organoplatinum Compounds; C570220:ethacraplatin; C081294:satraplatin; C484555:GSTA1 protein, human; D005982:Glutathione Transferase; D004976:Ethacrynic Acid