Table 2.

In vivo toxicity and efficacy data

TreatmentNadir body weight (% day 0)ToxicityMedian time to RTV4 (range), daysTumor growth delay% Enhancement
Saline control970/458 (6.5–11)
TMZ960/4524 (22–27)16
TMZ + AG14477 (1 mg/kg)990/530 (26–32)2237.5 ns
TMZ + AG14477 (10 mg/kg)950/531 (25–80)2343.8 na
TMZ + AG14418 (1 mg/kg)980/525 (15–33)176.3 ns
TMZ + AG14418 (10 mg/kg)950/532 (25–36)2450
TMZ + AG14361 (1 mg/kg)960/2032 (27–34)2450
TMZ + AG14361 (10 mg/kg)943/4536 (35–38.5)2875
TMZ + AG14584 (1 mg/kg)910/534 (20–40)2662.5 ns
TMZ + AG14584 (10 mg/kg)872/521 (21–25)13−18.8 ns
TMZ + AG14598 (1 mg/kg)950/535 (29–39)2768.8
TMZ + AG14598 (10 mg/kg)960/538 (36–42)3087.5
TMZ + MS AG14531 (1 mg/kg)*980/533 (31–34)2556.3
TMZ + MS AG14531 (10 mg/kg)951/533.5 (33–40)25.559.4
TMZ + AG14452 (1 mg/kg)940/530 (24–100)2237.5
TMZ + AG14452 (10 mg/kg)900/534 (31–53)2662.5
TMZ + MS AG14521 (1 mg/kg)970/536 (35–36)2875
TMZ + MS AG14521 (10 mg/kg)§901/541 (36–49)33106.3
TMZ + MS AG14644 (1 mg/kg)*912/533 (32–33)2556.3
TMZ + MS AG14644 (10 mg/kg)835/5n/a
TMZ + MS AG14451 (1 mg/kg)960/530 (29–46)2237.5
TMZ + MS AG14451 (10 mg/kg)§901/537 (36–38)2981.3
TMZ + MS AG14447 (0.1 mg/kg)960/532 (26–39)2450
TMZ + MS AG14447 (1 mg/kg)831/1041 (30–45)33106.3
TMZ + MS AG14447 (10 mg/kg)835/5n/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.