Tigapotide TFA

Copenhagen rats (male, inoculated s.c. into the right flank with MatLyLu-PTHrP cells)^[2]

1.0 μg/kg/day; 10 μg/kg/day; 100 μg/kg/day

s.c.; daily; up to 15 days

Caused a dose-dependent inhibition of MatLyLu-PTHrP tumor growth, with statistically significant tumor volume reductions at 10.0 μg/kg/day and 100.0 μg/kg/day compared to vehicle controls at Day 14 and Day 16.
Reduced tumoral PTHrP production in a dose-dependent manner, with the highest dose producing the most pronounced effect.
Reduced plasma PTHrP levels in a dose-dependent manner, with statistically significant reductions at 10.0 μg/kg/day and 100.0 μg/kg/day compared to vehicle controls, with levels falling to ~60 pmol equivalents/l and ~45 pmol equivalents/l, respectively.
Reduced plasma calcium levels in a dose-dependent manner, with statistically significant reductions at 10.0 μg/kg/day and 100.0 μg/kg/day compared to vehicle controls, with levels falling to ~4.0 mmol/l and ~3.6 mmol/l, respectively.
Induced tumor cell apoptosis as measured by DNA fragmentation and TUNEL assay.
Significantly delayed the development of hind-limb paralysis compared to vehicle controls, with a higher percentage of non-paralyzed animals remaining at Days 14, 15, and 16.
Exhibited a significant decrease in tumor burden in the lumbar vertebrae compared to vehicle controls.
Was more effective at delaying the development of skeletal metastases than equimolar concentrations of PSP-94.