e14090 Background: 4SC-207 is a novel small molecule with strong anti-mitotic activity. In this study the potency on in vitro cell proliferation, including chemotherapeutically resistant P-gp-expressing cells, was investigated. These observations were confirmed in in vivo xenograft tumor models. Methods: In vitro proliferation assay: 4SC-207 was tested on a panel of 50 ATCC cell lines. After a 24 h pre-growth period cells were incubated with 4SC-207 at different concentrations for 72 hours. After treatment cells were precipitated and stained with 0.4% wt/v sulforhodamine B solution in 1% acetic acid. Measurement of optical density was performed at 520 nm. Proliferation inhibition was determined as growth inhibition of 50% (GI50). In vivo xenograft model: 4SC-207 was tested both i.v. and p.o. in a xenograft NMRI mouse model using human colon adenocarcinoma cell line RKOp27. In the i.v. study 4SC-207 was administered at a dose of 40 mg/kg BID on days 1-7 and SID on days 8 and 11-14. In the p.o. study 4SC-207 was administered at a dose of 80 mg/kg SID on days 1, 2, 6, 7, 11, and 12. Endpoints consisted of tumor volume and body weight and hematologic parameters. Results: In vitro proliferation assay: 4SC-207 effectively inhibited the proliferation of most tested tumor cell lines with average GI50 values between 4 nM and 12 nM. 4SC-207 was also active on cell lines such as human colon cell lines HCT-15 and DLD-1 which display P-gp up-regulation and are known to be resistant to a large set of conventional anti-cancer agents (e.g. taxanes). In vivo xenograft model: 4SC-207 displayed a strong anti-tumor activity. Treatment with 4SC-207 induced complete tumor stasis (i.v.: Treated/Control = 0.09; p.o.: T/C = 0.1). Effects on body weight were mild and other signs of overt toxicity were not observed. Conclusions: 4SC-207 is a highly potent, novel anti-mitotic compound with strong in vitro and in vivo anti-tumor activity. 4SC-207 is also active on P-gp expressing tumor cells and offers the opportunity for treatment of hematological and solid tumor types which are resistant to standard anti-cancer agents.