In vivo toxicity and efficacy data
Treatment | Nadir body weight (% day 0) | Toxicity | Median time to RTV4 (range), days | Tumor growth delay | % Enhancement |
---|---|---|---|---|---|
Saline control | 97 | 0/45 | 8 (6.5–11) | ||
TMZ | 96 | 0/45 | 24 (22–27) | 16 | |
TMZ + AG14477 (1 mg/kg) | 99 | 0/5 | 30 (26–32) | 22 | 37.5 ns |
TMZ + AG14477 (10 mg/kg) | 95 | 0/5 | 31 (25–80) | 23 | 43.8 na |
TMZ + AG14418 (1 mg/kg) | 98 | 0/5 | 25 (15–33) | 17 | 6.3 ns |
TMZ + AG14418 (10 mg/kg) | 95 | 0/5 | 32 (25–36) | 24 | 50 |
TMZ + AG14361 (1 mg/kg) | 96 | 0/20 | 32 (27–34) | 24 | 50 |
TMZ + AG14361 (10 mg/kg) | 94 | 3/45 | 36 (35–38.5) | 28 | 75 |
TMZ + AG14584 (1 mg/kg) | 91 | 0/5 | 34 (20–40) | 26 | 62.5 ns |
TMZ + AG14584 (10 mg/kg) | 87 | 2/5 | 21 (21–25) | 13 | −18.8 ns |
TMZ + AG14598 (1 mg/kg) | 95 | 0/5 | 35 (29–39) | 27 | 68.8 |
TMZ + AG14598 (10 mg/kg) | 96 | 0/5 | 38 (36–42) | 30 | 87.5 |
TMZ + MS AG14531 (1 mg/kg)* | 98 | 0/5 | 33 (31–34) | 25 | 56.3 |
TMZ + MS AG14531 (10 mg/kg)† | 95 | 1/5 | 33.5 (33–40) | 25.5 | 59.4 |
TMZ + AG14452 (1 mg/kg) | 94 | 0/5 | 30 (24–100) | 22 | 37.5 |
TMZ + AG14452 (10 mg/kg) | 90 | 0/5 | 34 (31–53) | 26 | 62.5 |
TMZ + MS AG14521 (1 mg/kg)‡ | 97 | 0/5 | 36 (35–36) | 28 | 75 |
TMZ + MS AG14521 (10 mg/kg)§ | 90 | 1/5 | 41 (36–49) | 33 | 106.3 |
TMZ + MS AG14644 (1 mg/kg)* | 91 | 2/5 | 33 (32–33) | 25 | 56.3 |
TMZ + MS AG14644 (10 mg/kg)† | 83 | 5/5 | n/a | ||
TMZ + MS AG14451 (1 mg/kg)‡ | 96 | 0/5 | 30 (29–46) | 22 | 37.5 |
TMZ + MS AG14451 (10 mg/kg)§ | 90 | 1/5 | 37 (36–38) | 29 | 81.3 |
TMZ + MS AG14447 (0.1 mg/kg) | 96 | 0/5 | 32 (26–39) | 24 | 50 |
TMZ + MS AG14447 (1 mg/kg) | 83 | 1/10 | 41 (30–45) | 33 | 106.3 |
TMZ + MS AG14447 (10 mg/kg) | 83 | 5/5 | n/a |
NOTE: Temozolomide (200 mg/kg i.p.).
Abbreviations: TMZ, temozolomide; ns, not significant [All other % Enhancement values represent significant (P > 0.05) enhancement of temozolomide-induced tumour growth delay]; n/a, not analyzed (all mice died prior to RTV4).
↵* Mesylate salt dose equivalent parent compound = 0.78 mg/kg.
↵† Mesylate salt dose equivalent parent compound = 7.8 mg/kg.
↵‡ Mesylate salt dose equivalent parent compound = 0.79 mg/kg.
↵§ Mesylate salt dose equivalent parent compound = 7.9 mg/kg.