To discover novel drugs for neuroblastoma treatment, we have previously screened 
a panel of drugs and identified 30 active agents against neuroblastoma cells. 
Here we performed microarray gene expression analysis to monitor the impact of 
these agents on a neuroblastoma cell line and used the connectivity map (cMAP) 
to explore putative mechanism of action of unknown drugs. We first compared the 
expression profiles of 10 compounds shared in both our dataset and cMAP database 
and observed the high connectivity scores for 7 of 10 matched drugs regardless 
of the differences of cell lines utilized. The screen of cMAP for 
uncharacterized drugs indicated the signature of Epoxy anthraquinone derivative 
(EAD) matched the profiles of multiple known DNA targeted agents (topoisomerase 
I/II inhibitors, DNA intercalators, and DNA alkylation agents) as predicted by 
its structure. Similar result was obtained by querying against our internal 
NB-cMAP (http://pob.abcc.ncifcrf.gov/cgi-bin/cMAP), a database containing the 
profiles of 30 active drugs. These results suggest that Epoxy anthraquinone 
derivative may inhibit neuroblastoma cells by targeting DNA replication 
inhibition. Experimental data also demonstrate that Epoxy anthraquinone 
derivative indeed induces DNA double-strand breaks through DNA alkylation and 
inhibition of topoisomerase activity. Our study indicates that Epoxy 
anthraquinone derivative may be a novel DNA topoisomerase inhibitor that can be 
potentially used for treatment of neuroblastoma or other cancer patients.