Fig. 5. KL-50 (4a) appears to be safe and efficacious in both MGMT−/MMR+ and MGMT−/MMR− flank tumors over a wide range of treatment regimens and conditions.

(A) Xenograft LN229 MGMT−/MMR+ flank tumors treated with three weekly cycles of oral administration of 10% cyclodextrin control (n = 7 mice), TMZ (1a) (n = 7 mice, 5 mg/kg) or KL-50 (4a) (n = 6 mice, 5 mg/kg) on Monday, Wednesday, and Friday (individual spider plots in fig. S10A). (B) Xenograft LN229 MGMT−/MMR− flank tumors treated with three weekly cycles of oral administration of 10% cyclodextrin control (n = 6 mice), TMZ (1a) (n = 5 mice, 5 mg/kg), or KL-50 (4a) (n = 5 mice, 5 mg/kg) on Monday, Wednesday, and Friday (individual spider plots in fig. S10B). (C) Mean body weight of mice during LN229 flank tumor experiments in (A) and (B). (D to F) Xenograft (D) LN229 MGMT−/MMR+ and (E) LN229 MGMT−/MMR− flank tumors treated with oral administration of 10% cyclodextrin control (n = 7 mice), KL-50 (4a) (n = 6 mice, three cycles of 15 mg/kg on Monday, Wednesday, and Friday), KL-50 (4a) (n = 6 mice, 1 cycle of 25 mg/kg Monday through Friday), or intraperitoneal administration of KL-50 (4a) (n = 7 mice, three cycles of 5 mg/kg on Monday, Wednesday, and Friday) revealed equal efficacy with no observable increases in toxicity, (F) as measured with mice systemic weights (individual spider plots are provided in fig. S10C). (G) Xenograft LN229 MGMT−/MMR+ and LN229 MGMT−/MSH6− flank tumors with a larger average starting tumor size of ~400 mm³ and ~350 mm³, respectively, treated with three weekly cycles of oral administration of 10% cyclodextrin (n = 4 mice) or KL-50 (4a) (n = 4 mice, 25 mg/kg on Monday, Wednesday, and Friday). The study period was limited by control groups that had to be euthanized for exceeding the ethical maximum allowed tumor size, thus ending the study. In (A) to (G), points indicate the mean, and error bars indicate SEM; *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.