Irinotecan (CPT-11)

Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against a range of tumour types.  Irinotecan causes cell toxicity by stabilizing a ternary complex between the nuclear enzyme topoisomerase I (topo I) and double-stranded DNA, leading to single and double strand breaks. [Clin Exp Pharmacol Physiol. 1996 Oct-Nov;23(10-11):1000-4.]  TopoGEN provides this reagent as a control poison/inhibitor of topoisomerase I.    For in vitro cleavage detection, we recommend that the drug be tested over a wide range of uM concentrations; however, cleavages are strongly influenced by the amount of topoisomerase in the reaction as well as the type of assay being employed (SDSK+ vs. Radioactive End Labeled DNA vs. testing for plasmid cleavages).  Note that large amounts of enzyme will be required to detect cleavage complex, compared to assays that measure catalytic activity.