TY - JOUR
T1 - Third row transition metals for the treatment of cancer
AU - Johnstone, Timothy C.
AU - Suntharalingam, Kogularamanan
AU - Lippard, Stephen J.
PY - 2015/3/13
Y1 - 2015/3/13
N2 - 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 celldeath 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.
AB - 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 celldeath 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.
KW - Anti-cancer
KW - Monofunctional
KW - Osmium
KW - Platinum
KW - Transition metal
UR - http://www.scopus.com/inward/record.url?scp=84922553162&partnerID=8YFLogxK
U2 - 10.1098/rsta.2014.0185
DO - 10.1098/rsta.2014.0185
M3 - Article
AN - SCOPUS:84922553162
SN - 1364-503X
VL - 373
JO - PHILOSOPHICAL TRANSACTIONS- ROYAL SOCIETY OF LONDON SERIES A MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
JF - PHILOSOPHICAL TRANSACTIONS- ROYAL SOCIETY OF LONDON SERIES A MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
IS - 2037
ER -
