Rucaparib significantly potentiated TMZ-induced tumor regrowth delay in a flank tumor model of GBM12. Median time for tumor to exceed a 1000 mm3 size endpoint for placebo, TMZ, and TMZ/rucaparib treatment was 32, 86, and 121 days, p < 0.01, respectively. In contrast, the addition of rucaparib to TMZ therapy in GBM12 orthotopic xenografts was ineffective (median survival: placebo 16 days, TMZ 68 days and TMZ/rucaparib 81 days, p = 0.88. Therefore, subsequent studies focused on evaluating whether exclusion of rucaparib from the brain and orthotopic brain tumors might contribute to the lack of efficacy observed in the orthotopic xenograft models.
Cell Experiment | |
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Cell lines | GBM12 cell |
Preparation method | Cells were incubated with 2 −M rucaparib for 60 minutes at 37°C and then transport was quenched with cold PBS prior to lysis in 1% Triton X-100. Cell pellets were stored at −80°C until analysis using high-performance liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). |
Concentrations | 2 μM |
Incubation time | 24 h |
Animal Experiment | |
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Animal models | Mice with established intracranial xenografts |
Formulation | dissolved in dimethylsulfoxide and diluted in saline |
Dosages | 1 mg/kg |
Administration | i.v. |
Molecular Weight | 555.67 |
Formula | C10H16O4S.C19H18FN3O |
CAS Number | 1859053-21-6 |
Form | Solid |
Solubility (25°C) | 10 mM in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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