TY - JOUR
T1 - A quadruple-action platinum (IV) prodrug with anticancer activity against KRAS mutated cancer cell lines
AU - Petruzzella, Emanuele
AU - Braude, Jeremy Phillip
AU - Aldrich-Wright, Janice R.
AU - Gandin, Valentina
AU - Gibson, Dan
PY - 2017
Y1 - 2017
N2 - Abstract: We developed a novel PtIV prodrug that simultaneously releases four different bioactive moieties inside the cancer cell. Its cytotoxicity against monolayer cultures (2D) and spheroid (3D) cancer cells is significantly better than cisplatin. It is 200-450-fold more potent than cisplatin against KRAS mutated pancreatic and colon cancers and is 40-fold more selective towards KRAS mutated cells compared to noncancerous. This is important since RAS proteins play a role in regulating cell differentiation, proliferation, and survival and KRAS is mutated in 90% of pancreatic adenocarcinomas, 45%of colorectal cancers, and 35%of lung adenocarcinomas. The selectivity index, determined by dividing the IC50 value in non-cancerous cells by that of a cancerous cell line, is two-fold better than cisplatin, attesting to preferential cytotoxicity towards neoplastic cells.
AB - Abstract: We developed a novel PtIV prodrug that simultaneously releases four different bioactive moieties inside the cancer cell. Its cytotoxicity against monolayer cultures (2D) and spheroid (3D) cancer cells is significantly better than cisplatin. It is 200-450-fold more potent than cisplatin against KRAS mutated pancreatic and colon cancers and is 40-fold more selective towards KRAS mutated cells compared to noncancerous. This is important since RAS proteins play a role in regulating cell differentiation, proliferation, and survival and KRAS is mutated in 90% of pancreatic adenocarcinomas, 45%of colorectal cancers, and 35%of lung adenocarcinomas. The selectivity index, determined by dividing the IC50 value in non-cancerous cells by that of a cancerous cell line, is two-fold better than cisplatin, attesting to preferential cytotoxicity towards neoplastic cells.
KW - antineoplastic agents
KW - cancer cells
KW - platinum
KW - prodrugs
UR - http://hdl.handle.net/1959.7/uws:42998
U2 - 10.1002/anie.201706739
DO - 10.1002/anie.201706739
M3 - Article
SN - 1433-7851
VL - 56
SP - 11539
EP - 11544
JO - Angewandte Chemie (International Edition)
JF - Angewandte Chemie (International Edition)
IS - 38
ER -
