AZ32 is an orally bioavailable and blood-brain barrier-penetrating ATM inhibitor with an IC50 of <6.2 nM for ATM enzyme, and an IC50 of 0.31 uM for ATM in cell.
AZ32 is a next-generation blood-brain barrier (BBB)-penetrating ATM inhibitor. AZ32 blocks the DNA damage response and radiosensitized GBM cells in vitro[1].
AZ32, with enhanced BBB penetration, is highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse. 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[1].
References:
[1]. Karlin J, et al. Orally Bioavailable and Blood-Brain Barrier-Penetrating ATM Inhibitor (AZ32) Radiosensitizes Intracranial Gliomas in Mice. Mol Cancer Ther. 2018 Aug;17(8):1637-1647.