title: Third row transition metals for the treatment of cancer.
abstract: Platinum compounds are a mainstay of cancer chemotherapy, with over 50% of patients receiving platinum. But there is a great need for improvement. Major features of the cisplatin mechanism of action involve cancer cell entry, formation mainly of intrastrand cross-links that bend and unwind nuclear DNA, transcription inhibition and induction of cell-death programmes while evading repair. Recently, we discovered that platinum cross-link formation is not essential for activity. Monofunctional Pt compounds such as phenanthriplatin, which make only a single bond to DNA nucleobases, can be far more active and effective against a range of tumour types. Without a cross-link-induced bend, monofunctional complexes can be accommodated in the major groove of DNA. Their biological mechanism of action is similar to that of cisplatin. These discoveries opened the door to a large family of heavy metal-based drug candidates, including those of Os and Re, as will be described.
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Timothy C
authors: TC
authors: Johnstone
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Kogularamanan
authors: K
authors: Suntharalingam
authors: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA lippard@mit.edu.
authors: Stephen J
authors: SJ
authors: Lippard
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004260:DNA Repair; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000737:chemistry; D028561:Transition Elements / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D028561:Transition Elements; D010984:Platinum; D004247:DNA
keywords: anti-cancer; monofunctional; osmium; platinum; transition metal