Description
Intoplicine (RP 60475), an antitumor derivative in the 7H-benzo[e]pyrido[4,3-b]indole series, is a DNA topoisomerase I and II inhibitor. Intoplicine strongly binds DNA (K A = 2 x 10 5 /M) and thereby increases the length of linear DNAIn VitroWith 1-hour exposure to Intoplicine at final concentrations of 2.5 micrograms/mL and 10.0 micrograms/mL, 26% and 54% of the assessable specimens shows positive in vitro responses, respectively. With continuous exposure to Intoplicine at concentrations of 0.25 micrograms/mL and 2.5 micrograms/mL, 16% and 71% of the assessable specimens showed positive responses, respectively. Activity is seen against breast (71%), non-small-cell lung (69%), and ovarian (45%) cancer colony-forming units at a Intoplicine concentration of 10.0 micrograms/mL after 1-hour exposure. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoAt the highest non-toxic dose (HNTD) (6 mg/kg/injection, total dose, 36 mg/kg), Intoplicine shows highly active with a T/C of 0% and a corresponding total log cell kill of 3. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell AssayThe K562 human erythroleukemia cell line is established from a patient with chronic myelogenous leukemia. Cells are in the exponential growth phase at 5-8×10 5 in RPMI 1640 (GIBCO) supplemented with 10% fetal calf serum (Seromed) and 2 mM L-glutamine. Cell growth and viability are determined by phase contrast microscopy and by using the trypan blue test. Cells (2×10 6 ) are incubated with 1 µM Intoplicine for 1 h at 37°C, washed twice with PBS by centrifugation (200× g at 4°C) and resuspended in 200 µL PBS. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:Topoisomerase I Topoisomerase II