Rubitecan

Rubitecan is a DNA topoisomerase I inhibitor.^1,2 It inhibits DNA topoisomerase I and increases the fraction of supercoiled DNA in a cell-free assay in a concentration-dependent manner.¹ Rubitecan inhibits the growth of A121 ovarian and H460 lung cancer cells (IC₅₀s = 4 and 2 nM, respectively).³ It also inhibits the growth of doxorubicin-susceptible and -resistant MCF-7 breast cancer cells (IC₅₀s = 2 and 3 nM, respectively). Rubitecan (4 mg/kg twice per week) reduces tumor growth in a U937 leukemia mouse xenograft model.⁴

1.Rubin, E., Pantazis, P., Bharti, A., et al.Identification of a mutant human topoisomerase I with intact catalytic activity and resistance to 9-nitro-camptothecinJ. Biol. Chem.269(4)2433-2439(1994) 2.Hinz, H.R., Harris, N.J., Natelson, E.A., et al.Pharmacokinetics of the in vivo and in vitro conversion of 9-nitro-20(S)-camptothecin to 9-amino-20(S)-camptothecin in humans, dogs, and miceCancer Res.54(12)3096-3100(1994) 3.Bernacki, R.J., Pera, P., Gambacorta, P., et al.In vitro antitumor activity of 9-nitro-camptothecin as a single agent and in combination with other antitumor drugsAnn. N. Y. Acad. Sci.922293-297(2000) 4.Pantazis, P., Mendoza, J.T., Early, J.A., et al.9-Nitro-camptothecin delays growth of U-937 leukemia tumors in nude mice and is cytotoxic or cytostatic for human myelomonocytic leukemia lines in vitroEur. J. Haematol.50(2)81-89(1993)