Lookup NU author(s): Noel Monks,
Professor Nicola Curtin,
Dr Christine Arris,
Professor Herbie Newell
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Cellular determinants of sensitivity to the bifunctional alkylating agent 4-[N,N-bis(2-iodoethyl)amino]phenol (ZD2767D), the active drug produced by ZD2767 antibody-directed enzyme prodrug therapy (ADEPT), were studied. The prodrug 4-[N,N-bis(2-iodoethyl)amino]phenoxycarbonyl L-glutamic acid (ZD2767P)+activating enzyme carboxypeptidase G2 (CPG2) displayed growth inhibitory activity (IC50 0.04-2.2 μM) in colorectal tumour and non-small cell lung cancer (NSCLC) cell lines, and was more potent than a monofunctional ZD2767D analogue (colorectal cell lines - IC50 18-38 μM), synthesised for the first time. ZD2767P + CPG2 rapidly formed DNA-DNA interstrand cross-links (maximal at 10 min), and semi-quantitative analyses indicate that levels were similar in 3 of 4 cell lines studied (25-75 rad equivalents) at equitoxic (10×IC50/LC50) concentrations. In matched HCT116 TP53 functional/non-functional cell lines, there was no significant difference in the sensitivity to ZD2767P+CPG2. Together, these results suggest that cellular sensitivity to ZD2767P+CPG2 is, in part, related to the levels of interstrand crosslinks, but that TP53 status does not markedly effect chemosensitivity. © 2002 Elsevier Science Ltd. All rights reserved.
Author(s): Monks, N., Blakey, D., East, S., Dowell, R., Calvete, J., Curtin, N.J., Arris, C.E., Newell, D.R.
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Print publication date: 01/01/2002
ISSN (print): 0959-8049
ISSN (electronic): 1359-6349
PubMed id: 12110502
Altmetrics provided by Altmetric