Figure 5. LMP135 is the most potent fluoroindenoisoquinoline in the NCI-60 and shows antitumor activity in small cell lung cancer H82 xenografts model.

A, Comparison of the NCI-60 responses to the indicated TOP1 inhibitors. Each dot represents the growth inhibitory 50% concentration (GI₅₀) of a given NCI-60 cell line for the indicated drug. Data were obtained from the NCI Developmental Therapeutics Program (DTP). Average GI₅₀ for all 60 cell lines is indicated below the graph. LMP744 and LMP776 were not tested under 10 nM and LMP135 under 5 nM, and in those cell lines in which the GI₅₀ was less than the minimum concentration tested, the GI₅₀ values were recorded as 10 and 5 nM, respectively. The “averages” in these cases therefore represent mean-graph midpoint (MGM) values rather than true GI₅₀ averages. B, Comparison of the sensitivity of the NCI-60 cells to LMP135 vs. topotecan. GI₅₀ of each drug for each cell line is indicated as well as equipotency curve. LMP135 is approximately 10-fold more potent than topotecan. C-D, Antitumor activity of LMP135 (20 mg/kg) compared to topotecan (1.5 mg/kg) represented as tumor volume (C) or as Kaplan Meyer curves (D). Bars represent standard deviations (n = 10 for vehicle and topotecan; n = 6 for LMP135).