title: Understanding and improving platinum anticancer drugs--phenanthriplatin.
abstract: Approximately half of all patients who receive anticancer chemotherapy are treated with a platinum drug. Despite the widespread use of these drugs, the only cure that can be claimed is that of testicular cancer following cisplatin treatment. This article reviews some of our recent work on phenanthriplatin, a cisplatin derivative in which a chloride ion is replaced by phenanthridine, and on one of its analogues, the previously reported pyriplatin. These cationic complexes form monofunctional adducts on DNA that do not significantly distort the duplex, yet efficiently block transcription. Cell-based assays reveal altered cellular uptake properties and a cancer cell-killing profile different from those of established platinum drugs. Mechanistic work, including a crystal structure analysis of platinum-modified DNA in the active site of RNA polymerase II, is discussed herein.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Av., Cambridge, MA, 02139, U.S.A. lippard@mit.edu.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Johnstone
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Park
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010617:Phenanthridines / Q000627:therapeutic use*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010617:Phenanthridines
keywords: Cytotoxicity; RNA polymerase II; X-ray structure; monofunctional platinum; pyriplatin; review; transcription