AZ32 blocks the DNA damage response and radiosensitized GBM cells in vitro. AZ32 is highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. Following a single oral dose of AZ32 (200 mg/kg) in mice, the free-brain concentrations of AZ32 are in excess of the cellular IC50 for approximately 22 hours.
|Cell lines||U1242 cells|
|Preparation method||Human glioma U1242 cells were treated with AZ32 (3 μM) and radiation (2 Gy) or left untreated. At 48 hrs the cells were fixed and processed for ICC using anti-γ-tubulin (centrosomes) and -α-tubulin (microtubules). Cells were counterstained with DAPI to visualize nuclei.|
|Incubation time||48 h|
|Animal models||orthotopic GL261 glioma model (GL261/luc-red cells intracranially injected into C57bl6 mice)|
|Formulation||in hydroxypropyl-methyl cellulose (0.5%w/v)/0.1%w/v polysorbate-80 to 20 mg/ml|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||DMSO 70 mg/mL|
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